Fetal hemoglobin levels are related to metabolic control in diabetic subjects

We have investigated the relationship between fetal hemoglobin (HbF) levels and metabolic control in subjects with insulin-dependent (N = 79) and non-insulin-dependent diabetes mellitus (N = 242). HbF and hemoglobin A1c (HbA1c) levels were increased in subjects with type 1 and type 2 diabetes as compared to levels in nondiabetic individuals (P<0.0001), and were significantly higher in type 1 than in type 2 diabetes subjects. Lower levels of HbA1c and HbF were observed in type 2 diabetes subjects treated by diet, intermediate levels in those treated with oral hypoglycemic agents, and higher levels in those treated with insulin. HbF and HbA1c levels were correlated in type 1 diabetes (R2 = 0.57, P<0.0001) and type 2 diabetes (R2 = 0.58, P<0.0001) subjects. Following intense treatment, twelve diabetic patients showed significant improvement both in HbA1c and HbF values. We conclude that increased HbF levels reflect poor metabolic control in subjects with diabetes mellitus.

Specific insulin and proinsulin secretion in glucokinase-deficient individuals

Glucokinase (GCK) is an enzyme that regulates insulin secretion, keeping glucose levels within a narrow range. Mutations in the glucokinase gene cause a rare form of diabetes called maturity-onset diabetes of the young (MODY). An early onset (less than 25 years), autosomal dominant inheritance and low insulin secretion stimulated by glucose characterize MODY patients. Specific insulin and proinsulin were measured in serum by immunofluorimetric assays (IFMA) during a 75-g oral glucose tolerance test (OGTT). Two kindreds (SA and LZ) were studied and compared to non-diabetic unrelated individuals (control group 1) matched for age and body mass index (BMI). In one kindred, some of these subjects were also obese (BMI>26 kg/m2), and other family members also presented with obesity and/or late-onset NIDDM. The MODY patients were also compared to a group of five of their first-degree relatives with obesity and/or late-onset NIDDM. The proinsulin profile was different in members of the two MODY kindreds. Fasting proinsulin and the proinsulin/insulin ratio were similar in MODY members of kindred LZ and subjects from control group 1, but were significantly lower than in MODY members of kindred SA (P<0.02 and P<0.01, for proinsulin and proinsulin/insulin ratio, respectively). Moreover, MODY members of family SA had higher levels of proinsulin and proinsulin/insulin ratio, although not significantly different, when compared to their first-degree relatives and to subjects from control group 2. In conclusion, we observed variable degrees of proinsulin levels and proinsulin/insulin ratio in MODY members of two different kindreds. The higher values of these parameters found in MODY and non-MODY members of kindred SA is probably related to the obesity and late-onset NIDDM background present in this family.