ABSTRACT
Type 2 diabetes, one of the most frequent chronic diseases, has an important effect on bone metabolism, with most studies reporting an increased prevalence of fractures in these patients despite an apparently increased bone mineral density. Most probable explanation is an alteration of bone structure/quality with increased fragility but the different diabetes medications influence the risk of fracture. While metformin and incretin-based therapies are safe, thiazolidinediones and canagliflozin (sodium-glucose cotransporter-2 inhibitor) negatively impact bone metabolism and should be avoided in subjects at increased risk of fractures. Insulin and sulphonylureas are generally safe but can increase the risk of hypoglycemia and falls with subsequent traumatic fractures. Their combination should be avoided, especially in elderly subjects.
ABSTRACT
Type 1 diabetes (T1DM) is a common, chronic disease with autoimmune pathogeny, conditioned by genetic factors. Class II HLA DR and DQ and insulin gene polymorphisms encode for most of the T1DM genetic susceptibility. We have previously shown that class I alleles of the insulin gene INS-VNTR locus are strongly associated with T1DM in the Romanian population. The aim of our study was to confirm the contribution of INS-VNTR to T1DM genetic susceptibility in Romania. For this we typed the insulin gene -23HphI A/T polymorphism (an accurate marker for the INS-VNTR alleles) on 219 Romanian T1DM families using Taqman. Allele transmission to diabetics and unaffected siblings was assessed using the Transmission Disequilibrium Test (TDT). We found a significantly increased transmission of -23HphI A allele to diabetics (78.31% transmission, pTDT = 2.4 e-07) which confirms our previous findings. Combined with the data from the first 204 Romanian T1DM families, the transmission of -23HphI A allele to diabetics is almost 80% (79.78%, pTDT = 2.8 e-15). This percentage indicates the same level of predisposition as for the most diabetogenic HLA's. In conclusion, our results indicate an exceptionally strong association of the class I INS-VNTR alleles with T1DM for the Romanian population.
