Prevalence and comorbidities of double diabetes.

BACKGROUND: A growing number of people with type 1 diabetes (T1DM) are identified with features of metabolic syndrome (MS) known as "double diabetes", but epidemiologic data on the prevalence of MS in T1DM and its comorbidities are still lacking. Aim of this cross sectional study is to better estimate the prevalence of MS in T1DM, and to assess its association with comorbidities. METHODS: Data of 31,119 persons with autoimmune diabetes mellitus were analysed for signs of MS and presence of late complications. Double diabetes was defined as T1DM coexisting with MS (obesity, hypertension, dyslipidemia). Multiple linear or logistic regression analyses were performed to identify associations between double diabetes and late complications. RESULTS: 25.5% (n=7926) of persons with T1DM presented additionally the MS. Persons with double diabetes showed significantly more macrovascular comorbidities (coronary heart disease 8.0% versus 3.0% w/o MS, stroke 3.6% versus 1.6%, diabetic foot syndrome 5.5% versus 2.1%). Also microvascular diseases were increased in people with double diabetes (retinopathy 32.4% versus 21.7%, nephropathy 28.3% versus 17.8%). Both macrovascular and microvascular comorbidities were increased independent of glucose control, even if patients with good metabolic control (HbA1c <7.0%, 53mmol/mol) showed significantly less macrovascular (coronary heart disease 2.3% versus 1.8%, p<0.0001) and microvascular problems (retinopathy 8.7% versus 6.6%, p<0.0001). CONCLUSIONS: Double diabetes seems to be an independent and important risk factor for persons with T1DM in developing macrovascular and microvascular comorbidities. Therefore, patients should be identified and development of MS should be avoided. Longterm studies are needed to observe the effect of insulin resistance on patients with autoimmune diabetes.

The broad clinical phenotype of Type 1 diabetes at presentation.

Immune-mediated (auto-immune) Type 1 diabetes mellitus is not a homogenous entity, but nonetheless has distinctive characteristics. In children, it may present with classical insulin deficiency and ketoacidosis at disease onset, whereas autoimmune diabetes in adults may not always be insulin dependent. Indeed, as the adult-onset form of autoimmune diabetes may resemble Type 2 diabetes, it is imperative to test for diabetes-associated autoantibodies to establish the correct diagnosis. The therapeutic response can be predicted by measuring the levels of autoantibodies to various islet cell autoantigens, such as islet cell antibodies (ICA), glutamate decarboxylase 65 (GAD65), insulin, tyrosine phosphatase (IA-2) and IA-2ß, and zinc transporter 8 (ZnT8) and evaluating ß-cell function. A high risk of progression to insulin dependency is associated with particular genetic constellations, such as human leukocyte antigen risk alleles, young age at onset, the presence of multiple autoantibodies, including high titres of anti-GAD antibodies; such patients should be offered early insulin replacement therapy, as they respond poorly to diet and oral hypoglycaemic drug therapy. Hence, considering the broad spectrum of phenotypes seen in adult-onset diabetes, treatment targets can only be reached by identification of immune-mediated cases, as their management differs from those with classical Type 2 diabetes.