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

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

Assessment of thyroid function and autoantibody in type 2 diabetes mellitus

The associations between type 1 diabetes mellitus [DM] and autoimmune thyroid disease and other autoimmune diseases have long been recognized. However, these associations in type 2 DM are not certain. The study was performed to assess the thyroid function and autoimmune thyroiditis by detection of thyroglobulin antibodies [TG-ab] and thyroid peroxidase antibodies [TPO-ab] in type 2 diabetes mellitus. The study included 50 patients with type 2 diabetes over 10 years duration and 20 control subjects. The study was performed at Al-Azhar University Hospitals for control or management of diabetic complications. Patients with non-thyroidal illness or drug therapy, which known to affect thyroid functions were excluded from the study. The subjects of this study were submitted to the following: complete history and clinical examination, BMI, blood sugar, lipid profile, thyroid function test [FT3, FT4, and TSH], HbAlc and thyroid autoantibodies [Tg-ab and TPO-ab]. Twenty-six patients out of 50 having abnormal levels of TSH, 6 of them below the normal reference range, while the other 18 patients with elevated TSH levels. Patients with elevated TSH had significantly lowered serum FT3, FT4 and elevated levels of TPO-ab, TG-ab, HbAlc, disease duration and BMI when compared to those with normal TSH [p<0.01, for all]. Patients with decreased levels of TSH had significantly elevated levels of FT3, FT4, HbAlc and BMI when compared to those with normal TSH [p<0.01], but no significant changes were found in serum levels of autoantibodies. Interestingly the incidence of abnormal thyroid function and elevated thyroid auto-antibodies were significantly higher in patients treated by insulin [70%] versus those treated by oral hypoglycemic drugs [30%], [p<0.01]. Twenty two patients out of 50 [44%] had elevated TPO-ab levels, 13 of them have TSH abnormality, 12 of these 13 patients have subclinical hypothyroidism and one has subclinical hyperthyroidism. 25 patients of 50 [50%], have increased level of TG-ab, 18 of them have abnormal TSH values, 16 out of these 18 have subclinical hypothyroidism and two patients have subclinical hyperthyroidism. Serum level of TSH only was significantly higher in females than males [p<0.05]. Serum levels of autoantibodies were correlated positively with serum levels of TSH, BMI, HbAlc, disease duration and insulin therapy and correlated negatively with FT3 and FT4. Type 2 diabetes may be associated with alteration in thyroid function especially subclinical hypothyroidism that is not fully explained by the mere presence of antithyroid antibodies