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Glucose fluxes and oxidation after an oral glucose load in patients with non-insulin-dependent diabetes mellitus of variable severity

par Fery, Françoise ;Melot, Christian ;Balasse, Edmond
Référence Metabolism, clinical and experimental, 42, 4, page (522-530)
Publication Publié, 1993

Article révisé par les pairs

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Résumé :

The relative contribution of liver and peripheral tissues to the postprandial glucose response has been examined in 19 obese non-insulin- dependent diabetes mellitus (NIDDM) patients and 11 matched nondiabetic control subjects during a 5-hour oral glucose tolerance test (OGTT) performed with a load of 75 g, corresponding to approximately 67 g/1.73 m2. A dual- tracer technique was used to measure exogenous and endogenous glucose fluxes separately. Glucose oxidation was measured by indirect calorimetry. Diabetic patients were subdivided into two subgroups designated as 'mild' (n = 7) and 'severe' (n = 12) NIDDM according to postabsorptive glucose concentration with a cut-off point of 140 mg/dL. In the basal state, glucose concentrations averaged 99, 117, and 194 mg/dL, respectively, in control subjects and in the two diabetic subgroups, but insulin concentrations were not significantly different between groups. In comparison to control subjects, the basal hyperglycemia of mildly diabetic patients was entirely caused by a reduced metabolic clearance rate (118 v 144 mL/min; P < .05), whereas in severely diabetic patients basal hyperglycemia resulted from a combination of increased hepatic glucose output (187 v 139 mg/min; P < .001) and decreased metabolic clearance rate (97 v 144 mL/min; P < .001). A similar situation prevailed during the initial 2 hours after glucose ingestion. In patients with mild NIDDM, glucose concentration increased by 121 ± 10 mg/dL as compared with 36 ± 7 mg/dL in control subjects (P < .001). This difference was entirely due to a reduction in tissue glucose uptake (31 ± 2 v 42 ± 3 g/2 hours; P < .005), with the rates of total glucose appearance (R(a)) being almost identical in the two groups (43 ± 2 v 46 ± 3 g/2 hours; NS). Average 0- to 2-hour insulin levels were not significantly different between diabetic and control subjects (73 ± 16 v 92 ± 10 μU/mL; NS). On the other hand, in severely diabetic patients in whom the integrated 0- to 2-hour insulin levels were markedly decreased (36 ± 3 v 92 ± 10 μU/mL; P < .001), the excessive increase in glycemia (+158 mg/dL at 2 hours) was accounted for in similar proportions by higher rates of total glucose entry (53 ± 2 v 46 ± 3 g/2 hours; P < .01) and decreased tissular disposal (33 ± 2 v 42 ± 3 g/2 hours; P < .005). The elevated total glucose entry rate was solely related to higher rates of residual hepatic glucose output (15 ± 1 v 8 ± 1 g/2 hours; P < .001), with the R(a) of exogenous glucose not being affected by the presence of diabetes. The reduction in uptake resulted in approximately equal proportion from an impairment in oxidative and nonoxidative disposal. The persistence of elevated levels of glucose and insulin in the diabetic patients beyond 2 hours allowed them to normalize their rates of glucose disposal and oxidation within the 5 hours following glucose ingestion. It is suggested from these data that during the transition from the normal state to overt NIDDM, reduced glucose tolerance is due initially to an impaired peripheral glucose disposal related mainly to peripheral insulin resistance. The additional participation of an impaired suppression of hepatic glucose output in the abnormal glycemic response could only be identified in a more severe diabetic state associated with a grossly deficient insulin response.