Metabolic studies in diabetes mellitus

Nattrass, Malcolm (1982) Metabolic studies in diabetes mellitus. University of Southampton, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

Diurnal rhythms of circulating concentrations of intermediary metabolites and hormones, and metabolite ratios were studied in normal subjects and patients with diabetes mellitus. In normal subjects, blood glucose concentration correlated poorly with concentrations of other intermediary metabolites. Significant relationships were found between blood lactate, pyruvate and alanine and significant negative correlations were observed between lactate or alanine and total ketone bodies. Glycerol correlated significantly with non-esterified fatty acids and total ketone bodies. In diabetic patients treated by dietary therapy blood glucose, pyruvate, alanine and triglyceride concentrations were significantly increased and blood glycerol and 3-hydroxybutyrate were significantly decreased compared with normal subjects. During sulphonylurea therapy well-controlled diabetics had significantly lower than normal lactate, pyruvate and glycerol concentrations. In contrast those with markedly elevated glucose had significant increases in lactate, pyruvate, alanine and glycerol. Diet or sulphonylurea treated patients had significantly higher circulating insulin concentrations than normal subjects implying insulin resistance. During biguanide therapy consistently elevated lactate, pyruvate, alanine and ketone body concentrations were observed. Lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios were also increased. Phenformin produced greater metabolic abnormalities than metformin. Insulin dependent diabetics treated by subcutaneous insulin regimens showed marked metabolic abnormalities. Consistent normoglycaemia was not observed. Significantly increased ketone bodies, lactate and pyruvate resulted from inappropriate insulin delivery. Considerable improvement was obtained during glucose controlled insulin infusion. It is concluded that in the majority of diabetic patients, current therapeutic regimens fail to correct abnormal metabolism and some, particularly biguanides and subcutaneous insulin regimens may increase abnormality.

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