Older women with diabetes have an increased risk of fracture: a prospective study

To determine whether type 2 diabetes is associated with fracture in older women, we analyzed data from 9654 women, age 65 yr or older, in the Study of Osteoporotic Fractures. Diabetes with age at onset 40 yr or older was reported by 657 women, of whom 106 used insulin. A total of 2624 women experienced at least one nonvertebral fracture during an average follow-up of 9.4 yr, and 388 had at least one vertebral fracture during an average interval of 3.7 yr. Although diabetes was associated with higher bone mineral density, it was also associated with a higher risk of specific fractures. Compared with nondiabetics, women with diabetes who were not using insulin had an increased risk of hip [relative risk (RR), 1.82; 95% confidence interval (CI), 1.24-2.69] and proximal humerus (RR, 1.94; 95% CI, 1.24-3.02) fractures in multivariate models controlling for age, body mass index, bone density, and other factors associated with fractures and diabetes. Insulin-treated diabetics had more than double the risk of foot (multivariate adjusted RR, 2.66; 95% CI, 1.18-6.02) fractures compared with nondiabetics. This study indicates that diabetes is a risk factor for hip, proximal humerus, and foot fractures among older women, suggesting that fracture prevention efforts should be a consideration in the treatment of diabetes.     

The multiple origins of Type 1 diabetes

It is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic β‐cells, eventually leading to β‐cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune‐mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen‐specific responses in patients with recent onset diabetes and subjects with pre‐diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new‐onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and β‐cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re‐evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of β‐cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms.     

Addressing insulin resistance in Type 1 diabetes

Type 1 diabetes is recognised to include an element of insulin resistance. Insulin resistance is an independent risk factor for the development of macro‐ and microvascular complications of Type 1 diabetes and may also contribute to the development of the disease. This understanding comes at a time when the incidence of Type 1 diabetes appears to be rising and the public health burden from its vascular complications is high. A variety of safe and efficacious manoeuvres are available to redress insulin resistance in Type 2 diabetes. So far however, clinical trials addressing insulin resistance in Type 1 diabetes have been small with only short periods of follow‐up. Regardless, these trials have yielded promising results. This review examines the evidence for insulin resistance in the pathophysiology of Type 1 diabetes and its complications, the problems associated with its measurement, and summarizes the trials aimed at reducing insulin resistance in Type 1 diabetes. This includes a meta‐analysis of controlled trials of adjuvant metformin in Type 1 diabetes.     

Clustering of microvascular complications in Type 1 diabetes mellitus

Aims

To describe to what extent microvascular complications exhibit clustering in persons with Type 1 diabetes, and to assess whether the presence of one complication modified the strength of the association between the other two.

Fibrinogen and factor VII levels improve with glycemic control in patients with type 1 diabetes mellitus who have microvascular complications

To determine whether the hypercoagulable state of patients with complications of diabetes can be reversed toward normal, a group of insulin-dependent individuals with proteinuria was treated with intensive insulin protocols. A statistically significant (P<.001) improvement in control of diabetes was achieved (mean +/- SEM glycosylated hemoglobin, 9.51% +/- 0.35% at baseline to 8.36% +/- 0. 39% at 12 months; and mean +/- SEM advanced glycosylated end products, 14.8 +/- 2.8 U/mL at baseline to 8.4 +/- 1.5 U/mL at 12 months). There were statistically significant decreases in 2 procoagulant factors: mean +/- SEM baseline elevated plasma factor VII, 128.69% +/- 5.63% at baseline to 106.24% +/- 3.43% at 12 months (P =.002); and mean +/- SEM plasma fibrinogen, 12.3 +/- 0.7 micromol/L (417.3 +/- 24.7 mg/dL) at baseline to 10.2 +/- 0.7 micromol/L (348.8 +/- 22.6 mg/dL) at 12 months (P =.04). Throughout the study, lipid fractions did not change significantly. Because plasma factor VII and fibrinogen concentrations were elevated while cholesterol and triglyceride concentrations were not, more attention should be paid to procoagulants as markers for thromboembolic complications in diabetic patients undergoing intensive insulin therapy.