Study of some endogenous factors and hormones contributing in the pathogenesis of ketosis in obese versus lean type 2 diabetes mellitus

ABSTRACT

Diabetic Ketoacidosis [DKA], resulting from severe insulin deficiency, accounts for most hospitalization in type 1 DM. However, the frequency, distinguishing features and pathogenesis of this syndrome in type 2 DM remain to be defined. The study was performed to evaluate the role of some endogenous factors and hormones contributing in the vulnerability of some type 2 DM that developed DKA easily than other. The study was conducted on 80 known type 2 diabetic patients [45 males and 35 females], 48 of them were obese body mass index [BMI] > 30 kg/m[2], admitted to Al-Azhar University Hospitals [emergency department] with manifestations of DKA [group I] from July 2003 to January 2005, and 20 type 2 diabetic patients of the same duration of DM, without history of DKA, [group II] with age and sex matched [12 males and 8 females], 10 of them were obese, as controls. After complete clinical examination and routine laboratory investigations, which confirm the diagnosis of DKA, the following investigations were studied; serum glucagon, C-peptide, glutamic acid decarboxylase antibody [GAD-ab], and C-peptide / glucagon ratio, random blood sugar [RBS], renal and liver function tests, arterial blood gases [bicarbonate and pH], serum electrolyte [sodium, potassium and chloride], lipid profile, CBC, complete urine analysis with special attention to level of ketone bodies Serum levels of glucagon, RBS and urine ketone were significantly higher in-group I than group II, while serum levels of C-peptide, C-peptide / glucagon ratio, sodium, potassium, and bicarbonate were significantly lower in-group I than group II. On the other hand no significant differences in the age, sex, disease duration, GAD abs, lipid profile, blood pH and serum chloride between group I and II. In patients with DKA, the age, disease duration, C-peptide, glucagon and C-peptide / glucagon ratio were significantly lower in lean than obese parents [p<0.05] for all. While serum levels of GAD-abs were significantly higher in lean than obese patients [p<0.05]. Interestingly in patients without DKA, serum levels of C-peptide were significantly lower [p<0.05], while serum levels of GAD-abs were significantly higher in lean than obese patients [p<0.05] and no significant changes in other parameters between them. On the other hand C-peptide correlated negatively with glucagon [r=-650] and GAD abs [r=-684], while serum glucagon correlated positively with GAD-abs [r=644]. It could be concluded that the pathogenesis of ketosis in type 2 diabetes is triggered mainly by deficient endogenous insulin in lean patients [had a criteria of type 1 diabetes such as; younger age of onset of DKA short duration of disease, elevated GAD-abs and low C-peptide / glucagon ratio but still classified as type 2diabetes] and relative increase glucagon level activity in obese patietrts. However, the C-peptide / glucagon ratio is the main denominator or determinant factor for ketosis in type 2 diabetes mellitus