A 65-year-old man comes to the physician because of a non-healing ulcer on his right foot. His past medical history is significant for recurrent high blood glucose readings for the last several years, because he has failed to comply with appropriate treatment. His BMI is 37 kg/m². Physical examination is significant for a bilateral symmetric decrease in vibration sensation over the feet and ankles. Which of the following is most likely to be associated with this patient's condition?

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The patient described in this vignette has type 2 diabetes mellitus (advanced age, obesity, prolonged non-compliance with treatment without immediate life-threatening consequences). The two cardinal defects involved in the pathophysiology of type 2 diabetes mellitus are increased insulin resistance and defective insulin secretion. Although still controversial, many researchers believe that increased insulin resistance is the primary abnormality in type 2 diabetes mellitus. Early in the pathogenesis of type 2 diabetes, glucose tolerance is thought to remain normal because of a compensatory increase in insulin secretion from beta cells. This compensatory insulin response by beta cells ultimately fails, causing poor glucose tolerance. A number of genetic and acquired factors are implicated in the beta-cell dysregulation of type 2 diabetes. Islet amyloid polypeptide (amylin) is one factor thought to be responsible for this beta cell dysfunction. Amylin is stored in insulin secretory granules and is co-secreted with insulin from pancreatic beta cells. Deposits of amylin are universally seen in the pancreatic islets of patients with type 2 diabetes mellitus. Amylin may play a causative role in beta cell apoptosis and defective insulin secretion; however, this theory is still controversial. Type 1 and type 2 diabetes mellitus have very strong genetic components. Twin studies have shown a concordance rate of 50% in identical twins for diabetes mellitus type 1, and around 80% for diabetes mellitus type 2. The genes involved in the pathogenesis of diabetes mellitus type 2 remain largely unknown. Gene polymorphism within the major histocompatibility complex contributes to type 1 diabetes mellitus disease in humans. HLA-DQ and -DR are the most important determinants of type 1 diabetes mellitus. In the general population, DR3 and DR4 are seen in approximately 40% of subjects; however, in patients with type 1 diabetes mellitus, DR3 and DR4 haplotypes are seen in more than 90% of subjects. (Choices A, C, D & E) These are features of type 1 diabetes mellitus. Type 1 diabetes occurs when an autoimmune response is triggered by an environmental insult in genetically susceptible individuals. Patients with type 2 diabetes retain at least some beta cell function, but patients with type 1 diabetes mellitus develop absolute deficiency of insulin secondary to immune destruction of pancreatic beta cells. These patients need insulin for survival. Discontinuation of insulin treatment results in ketoacidosis. Educational objective: Pancreatic islet amyloid deposition is characteristic of type 2 diabetes mellitus. A strong linkage with HLA class II gene makeup, pancreatic islet infiltration with leukocytes (insulitis), and antibodies against islet antigens are frequently seen in type 1 diabetes. __________ References: Evidence for proteotoxicity in beta cells in type 2 diabetes: toxic islet amyloid polypeptide oligomers form intracellularly in the secretory pathway. (http://www.ncbi.nlm.nih.gov/pubmed/20042670)

A 65-Year-Old Man Comes to the Physician Because of a Non-Healing