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Diabetes, More on Merde, the Microbiome, and the Dung Beetle

      There is both good and bad news. A piece of good news is that new approaches are making clinically meaningful inroads into the care and treatment of patients with diabetes mellitus (DM). For example, a new combination oral product that combines a sodium-glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase-4 (DPP-4) inhibitor is now available for adults with type 2 DM. A 5-arm study found that the combination was more effective than either drug alone in patients who did not do well on metformin as sole therapy. Reduction in glycosylated hemoglobin concentrations was the end point.
      • DeFronzo R.A.
      • Lewin A.
      • Patel S.
      • et al.
      Combination of empagliflozin and linagliptin as a second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin.
      Furthermore, the combination was less expensive than taking the 2 constituents separately.

      Med Lett Drugs Ther. Glyxambi - A new combination for type 2 diabetes. 2015 Apr 27;57(1467):65-66

      An element of bad news is that expenditures for pharmaceuticals for DM care increased in 2014, according to the IMS Institute for Healthcare Informatics; they reported an increase of 30.5% to a total of $32.2 billion (USD) in 2014, adding that this increment was “…driven by innovation and partially offset by off-invoice discounts and rebates, resulting in net spending growth of 22.4%.”

      IMS Institute for Healthcare Informatics. A review of the use of medicines in the U.S. in 2014 -- medicines use and spending shifts. April 2015. Available at: http://www.IMSHealth.com. Accessed May 14, 2015.

      This issue of Clinical Therapeutics highlights a group of papers invited by Dr. John G. Ryan, our topic editor for endocrinology, diabetes, and other endocrine disorders, which focuses on new research in DM.
      • van Olden C.
      • Groen A.K.
      • Nieuwdorp M.
      Role of intestinal microbiome in lipid and glucose metabolism in diabetes mellitus.
      • Katalenich B.
      • Shi L.
      • Liu S.
      • et al.
      Evaluation of a remote monitoring system for diabetes control.
      • Wang L.
      • Sawhney M.
      • Zhao Y.
      • et al.
      The association between colchicine use and risk of diabetes among Veterans Affairs population with gout.
      • Desouza C.V.
      • Gupta N.
      • Patel A.
      Cardiometabolic effects of new class of antidiabetic agents.
      • Ascher-Svanum H.
      • Chen Y.-F.
      • Hake A.
      • et al.
      Cognitive and functional decline among mild Alzheimer’s disease dementia patients with and without comorbid diabetes.
      Among them is a review by van Olden et al
      • van Olden C.
      • Groen A.K.
      • Nieuwdorp M.
      Role of intestinal microbiome in lipid and glucose metabolism in diabetes mellitus.
      on the microbiome and DM. Readers who regularly follow Clinical Therapeutics will note that we also focused on the microbiome in our May issue. (Before returning to the microbiome, I would like to take this opportunity to congratulate Dr. Ryan on his promotion to research professor.)
      I have been intrigued by research on the microbiome, as have others. Since our May issue, I have come across the writings of Ralph Lewin. In 1999, he published a book titled Merde.
      • Lewin R.A.
      Merde.
      In 2001, he published “More on Merde,”
      • Lewin R.A.
      More on Merde.
      a title I have borrowed for this editorial. I encourage all who are interested in the microbiome to read his latter publication. In particular, Lewin cites the ingestion of warm camel dung by Bedouins as a cure for dysentery. He suggests that an antibiotic compound, subtilisin, produced in the dung may have been the therapeutic entity. He also cites a book by J. Bernhardt on Bacillus subtilis that claims German soldiers in Africa during World War II also noted this beneficial effect. Bacillus subtilis, sometimes called grass or hay bacillus, is a gram-positive bacterium found not only in the soil and grasses but also in the intestinal tracts of humans and ruminants (ie, the camel). When grown in culture, it was a common way to treat intestinal tract diseases in America and Europe before the late 1940s. Since the discovery of newer antibiotics, its use has diminished, but it is still available in Middle Eastern countries as an alternative remedy.

      Bacillus subtilis. http://en.wikipedia.org/wiki/Bacillus_subtilis. Accessed May 15, 2015.

      The ingestion of the feces from another species is a type of coprophagia. Dogs, especially puppies, are well known to be coprophagic. Curiously, DM is one of the more common conditions found in adult dogs who are coprophagic.

      Coprophagia – what is it, and why do dogs do it? http://thedogtraininglady.com/coprophagia-what-is-it-and-why-do-dogs-do-it/. Accessed May 15, 2015.

      Human consumption of feces is considered to be a form of psychopathology, similar in some respects to pica. My only clinical experience with coprophagia was in the 1960s; the patient was a 26-year-old man impaired by severe mental retardation. At that time there was a paucity of literature on the cause of coprophagia; there has been little if any change since that time, perhaps because few want to think or write about this subject.
      The most notorious coprophagic species is the dung beetle, Scarabaeus sacer. The male and female beetles make balls from dung and roll them into burrowed holes. The female beetle then deposits her eggs onto these balls. Once the emerging larvae hatch, they feed on the dung. At the appropriate size and time, they climb out of these holes, and the life cycle proceeds.

      Ancient Egypt the mythology. http://www.egyptianmyths.net/scarab.htm. Accessed May 15, 2015.

      We do not know how the dung beetle, most often known as the sacred scarab, came to be seen as the symbol for Khepri (also called Khepera, Kheper, Khepra, or Chepri), the ancient Egyptian god linked to healing and new life (Figure).
      Figure thumbnail gr1
      FigureScarabaeus sacer. Photograph credit R. Shader.
      Khepri was thought to push the sun across the sky, leading to daily rebirth.

      Ancient Egypt the mythology. http://www.egyptianmyths.net/scarab.htm. Accessed May 15, 2015.

      On a visit to Egypt, I saw many depictions of Khepri, portrayed as a beetle pushing the sun (an orange orb). While trying to discover more about Khepri and the dung beetle, I came across a website that advertises the products of a company called Khepra Egyptian Skin Care.

      Khepra Egyptian Skin Care. http://www.khepra.com/Merchant5/merchant.mvc?Screen=ABOU. Accessed May 15, 2015.

      Khepra Egyptian Skin Care uses the scarab as its logo. Among its products is one called Khepra Foot Balm. Consistent with our focus, this product is claimed to be beneficial for patients with DM with foot care problems. Unfortunately, I was unable to reach the clinician cited as conducting the study that supports this claim.
      Finally, would you believe there is a Facebook site called Don’t Step in the Poop, a humorous site dedicated to self-help?

      Don’t Step in the Poop Facebook. https://www.facebook.com/dontstepinthepoop. Accessed May 15, 2015.

      Clinical Therapeutics will continue the push to clarify the role, if any, of the microbiome (aka, merde, poop) in DM (ie, the BM in DM) and other conditions.
      Endocrinology, Diabetes, and Other Endocrine Disorders Specialty Updates are published annually and are available as FREE ACCESS content on the journal’s website. The previous Specialty Update for this section, entitled “Diabetes Update,” was published in Volume 36, Number 4 of Clinical Therapeutics. To view the Diabetes Update, see the articles below:

      References

        • DeFronzo R.A.
        • Lewin A.
        • Patel S.
        • et al.
        Combination of empagliflozin and linagliptin as a second-line therapy in subjects with type 2 diabetes inadequately controlled on metformin.
        Diabetes Care. 2015; 38: 384-393
      1. Med Lett Drugs Ther. Glyxambi - A new combination for type 2 diabetes. 2015 Apr 27;57(1467):65-66

      2. IMS Institute for Healthcare Informatics. A review of the use of medicines in the U.S. in 2014 -- medicines use and spending shifts. April 2015. Available at: http://www.IMSHealth.com. Accessed May 14, 2015.

        • van Olden C.
        • Groen A.K.
        • Nieuwdorp M.
        Role of intestinal microbiome in lipid and glucose metabolism in diabetes mellitus.
        Clin Ther. 2015; 37: 1172-1177
        • Katalenich B.
        • Shi L.
        • Liu S.
        • et al.
        Evaluation of a remote monitoring system for diabetes control.
        Clin Ther. 2015; 37: 1216-1225
        • Wang L.
        • Sawhney M.
        • Zhao Y.
        • et al.
        The association between colchicine use and risk of diabetes among Veterans Affairs population with gout.
        Clin Ther. 2015; 37: 1206-1215
        • Desouza C.V.
        • Gupta N.
        • Patel A.
        Cardiometabolic effects of new class of antidiabetic agents.
        Clin Ther. 2015; 37: 1178-1194
        • Ascher-Svanum H.
        • Chen Y.-F.
        • Hake A.
        • et al.
        Cognitive and functional decline among mild Alzheimer’s disease dementia patients with and without comorbid diabetes.
        Clin Ther. 2015; 37: 1195-1205
        • Lewin R.A.
        Merde.
        Random House, New York1999
        • Lewin R.A.
        More on Merde.
        Perspect Biol Med. 2001; 44: 594-607
      3. Bacillus subtilis. http://en.wikipedia.org/wiki/Bacillus_subtilis. Accessed May 15, 2015.

      4. Coprophagia – what is it, and why do dogs do it? http://thedogtraininglady.com/coprophagia-what-is-it-and-why-do-dogs-do-it/. Accessed May 15, 2015.

      5. Ancient Egypt the mythology. http://www.egyptianmyths.net/scarab.htm. Accessed May 15, 2015.

      6. Scarab (artifact). http://en.wikipedia.org/wiki/Scarab_%28artifact%29. Accessed May 15, 2015.

      7. Khepra Egyptian Skin Care. http://www.khepra.com/Merchant5/merchant.mvc?Screen=ABOU. Accessed May 15, 2015.

      8. Don’t Step in the Poop Facebook. https://www.facebook.com/dontstepinthepoop. Accessed May 15, 2015.