Ketosis resistance in under thirty diabetic subjects

Young onset diabetic subjects in tropical developing countries include a group of subjects who exhibits a characteristic ketosis resistance termed as Malnutrition Related Diabetes Mellitus (MRDM) by the WHO Study Group. The mechanism for this resistance to ketosis is still uncertain. To understand this mechanism we have studied the serum responses of glucose, non-esterified fatty acid (NEFA) and triglyceride (TG) to intravenous fat emulsion in newly diagnosed 8 fibrocalculous pancreatic diabetes (FCPD) and 11 low insulin secretory (LIS) subjects under 30 years of age along with 27 age-matched Non Insulin Dependent Diabetes Mellitus (NIDDM) subjects. Overnight fasting subjects were given a 90 min infusion of intralipos 10% (2.5 mg/kg body weight/min) and serum was collected at 0, 60, 90, 120 and 150 min. The fasting NEFA in the 3 groups were almost similar (micromol/l, M +/- SEM: 486 +/- 58, 564 +/- 76 and 559 +/- 34 in FCPD, LIS and NIDDM respectively). Fasting TG also showed a close similarity among 3 groups (mg/dl, M+/-SEM: 117 +/- 11, 110 +/- 22 and 123 +/- 4 in FCPD, LIS and NIDDM respectively). Intravenous fat caused a steady rise of NEFA as well as TG in all groups during the 90 minutes of infusion followed by a gradual fall. No two groups significantly differed regarding NEFA and TG at any time point. Fasting glucose was markedly higher in FCPD (22.9 +/- 2.5, mmol/l, M+/-SEM) and LIS (20.8 +/- 1.6) than NIDDM (11.0 +/- 1.0). In all the 3 groups glucose showed a slow but steady fall. Fasting C-peptide was very low in FCPD (0.42 +/- 0.08, ng/ml, M +/- SEM) and LIS (0.55 +/- 0.09) whereas it was within normal range in NIDDM patients (2.99 +/- 0.24). The results suggest the following: (a) Depleted body fat store do not lead to a decreased supply of NEFA in FCPD and LIS subjects at the fasting state; (b) Increased supply of NEFA in these subjects lead to a normal esterification response as evidenced by a parallel rise of TG; (c) Inspite of markedly low level of the antilipolytic hormone insulin, FCPD and LIS subjects are capable to maintain NEFA and TG responses similar to NIDDM subjects. This may indicate that factor (s) other than substrate and esterification is (are) probably involved in the ketosis resistance of FCPD and LIS subjects; and (d) Although FCPD and LIS differ regarding generalized pancreatic damage (which raises the possibility of involvement of glucagon producing alpha-cells in the FCPD group) the two groups do not differ regarding the ketogenic substrate and esterfication responses.