ABSTRACT
OBJECTIVE: To develop and pilot a novel intervention addressing motivational and cognitive barriers to avoiding hypoglycemia in people with type 1 diabetes and persistent impaired awareness of hypoglycemia (IAH) despite training in flexible insulin therapy. RESEARCH DESIGN AND METHODS: A 6-week intervention using motivational interviewing and cognitive behavioral techniques was designed. Diabetes educators were trained and supported in its delivery to 23 people with IAH (Gold score ≥4). RESULTS: Twelve months postcourse, hypoglycemia awareness had improved (P < 0.001). Median (range) rates of severe hypoglycemia (SH) fell from 3 (0-104) to 0 (0-3) per person per year (P < 0.0001) and moderate from 14 (0-100) to 0 (0-18) per person per 6 weeks (P < 0.001). Worry and behavior around hyperglycemia improved. HbA1c was unchanged. CONCLUSIONS: A pilot intervention targeting motivation and cognitions around hypoglycemia engaged patients with resistant IAH and recurrent SH and was associated with significant improvement, supporting the hypothesis that these factors underpin problematic hypoglycemia.
Subject(s)
Awareness , Cognitive Behavioral Therapy/methods , Diabetes Mellitus, Type 1/therapy , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Patient Education as Topic/methods , Adult , Anxiety , Diabetes Mellitus, Type 1/psychology , Female , Health Knowledge, Attitudes, Practice , Humans , Hyperglycemia/drug therapy , Hypoglycemia/chemically induced , Insulin/therapeutic use , Male , Middle Aged , Motivational Interviewing , Pilot ProjectsABSTRACT
Tetrahydrofolates are essential cofactors for DNA synthesis and methionine metabolism. Malaria parasites are capable both of synthesizing tetrahydrofolates and precursors de novo and of salvaging them from the environment. The biosynthetic route has been studied in some detail over decades, whereas the molecular mechanisms that underpin the salvage pathway lag behind. Here we identify two functional folate transporters (named PfFT1 and PfFT2) and delineate unexpected substrate preferences of the folate salvage pathway in Plasmodium falciparum. Both proteins are localized in the plasma membrane and internal membranes of the parasite intra-erythrocytic stages. Transport substrates include folic acid, folinic acid, the folate precursor p-amino benzoic acid (pABA), and the human folate catabolite pABAG(n). Intriguingly, the major circulating plasma folate, 5-methyltetrahydrofolate, was a poor substrate for transport via PfFT2 and was not transported by PfFT1. Transport of all folates studied was inhibited by probenecid and methotrexate. Growth rescue in Escherichia coli and antifolate antagonism experiments in P. falciparum indicate that functional salvage of 5-methyltetrahydrofolate is detectable but trivial. In fact pABA was the only effective salvage substrate at normal physiological levels. Because pABA is neither synthesized nor required by the human host, pABA metabolism may offer opportunities for chemotherapeutic intervention.
