Longitudinal Study of Rhesus Monkeys Determines That Amylase and Lipase Levels Are Significant Risk Factors for Type 2 Diabetes Mellitus

Decreased levels of amylase have been reported in type 2 diabetes (T2DM), however, longitudinal within subject study ranging from healthy normal levels to preT2DM and overt DM has not previously been conducted in humans or in nonhuman primates. Rhesus monkeys provide the ideal subjects for this study as they are maintained under constant dietary and environmental conditions, and have, to date, been shown to have the same gastrointestinal/pancreas physiology and pathophysiology as humans. They frequently develop T2DM spontaneously and naturally, with no experimental intervention, and with life time rates of T2DM estimated to be 20 to 30 %. Adult rhesus monkeys were studied for a minimum of 3 years and a maximum of 20 years, with a minimum of 2 metabolic parameter measurements per year. These parameters included fasting plasma glucose (FPG), fasting plasma insulin (FPI), complete blood chemistry, and lipid profiles. Body fat was determined by the tritiated water dilution method or by the dual energy xray absorptiometry (DEXA). Insulin sensitivity was quantified by the euglycemic hyperinsulinemic clamp method. These parameters were used to identify the phases in the progression of monkeys from normal to overt diabetes as follows: normal = phases 1–3; metabolic syndrome = phases 4–6, impaired glucose tolerance= phase 7, and overt type 2 diabetes = phase 8. Diabetic monkeys requiring insulin treatment were excluded from this study. Human criteria were used to define MetSyn, IGT and T2DM. Normal healthy serum amylase levels were determined for the first time and shown to be 253 ±5.1 U/L for adults 7 to 11 yrs old (“human years” about 21 to 35 yrs), with normal lipase levels of 29.7± 1.6 U/L. Serum amylase levels declined with age by about 25%, with no change in serum lipase levels with age. In those that progressed through phases 4 to 8 reaching overt type 2 diabetes, serum amylase showed significantly greater declines from ages 13 to 20 yrs with progressive and parallel declines in metabolic parameters, including insulin sensitivity, and HDL cholesterol levels and increases in serum triglycerides and subsequently increases in fasting plasma glucose. The significant rise in serum triglycerides and the decline in amylase together serve as excellent early predictors of the progression to overt T2DM. These risk factors were highly predictive of both early and late onset diabetes. The lower amylase levels observed previously in people with diabetes were clearly not a consequence of diabetes, but were in fact markers of impending diabetes. Such biomarkers are likely to be useful in predicting the development of T2DM in patients years before the disease becomes overt. This study was carried out in accord with the FASEB principles for the use of animals in research. Support or Funding Information The work was supported by NIA N01AG31012 and NIA HHSN2532008002C to BCH, and the Department of Health Research, Government of India Human Resources Development Fellowship to UKC. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .