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The evolution of diabetes in non human primates: comparative physiology implications for human type 2 diabetes mellitus (T2DM)
Author(s) -
Hansen Barbara Caleen
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1055.10
Subject(s) - prediabetes , dyslipidemia , diabetes mellitus , glycemic , medicine , type 2 diabetes , endocrinology , type 2 diabetes mellitus , insulin , physiology
T2DM develops naturally and spontaneously in humans and non human primates. We have studied prospectively a colony of >220 adult rhesus monkeys that were continuously maintained with ad libitum feeding of a high fiber low fat “healthy” diet throughout life. 87 individuals were identified that developed frank T2DM. Longitudinal analysis of the emerging dysglycemia and dyslipidemia has allowed the determination of the glycemic threshold for diagnosis (dx) of prediabetes: 80 mg/dl (4.4 mmol/L) for monkeys, shown by modeling to be comparable to 100 mg/dl (5.5 mmol/L) in humans; and overt DM dx occurs at 100 mg/kg (5.5 mmol/L) in monkeys compared to the current ≥126 mg/dl (6.9 mmol/L) defined for humans. All monkeys reaching the prediabetes diagnosis, if not intervened on to prevent progression, did in fact proceed to overt diabetes (2/3 in < 3 yrs; ~<10 yrs in humans). Sequence analysis to model the diabetes trajectory showed that acute beta cell response to glucose peaked 2 to 6 years prior to DM dx; fasting plasma insulin 1 to 4 yrs pre DM dx; and nearly all were hypertriglyceridemic 5 to 12 yrs pre DM dx. These carefully controlled studies show that in humans fasting insulin, β cell functional responses and dyslipidemia should be used to identify those progressing toward diabetes in order to implement true preventive strategies prior to β cell failure. Supported by: supported by NIA N01AG31012 and NIA HHSN2532008002C.