A 66-year-old obese Caucasian man presented to an academic Diabetes Center for advice regarding his diabetes treatment. His diabetes was diagnosed 10 years previously on routine testing. He was initially given metformin but when his control deteriorated, the metformin was stopped and insulin treatment initiated. The patient was taking 50 units of insulin glargine and an average of 25 units of insulin aspartate pre-meals. He had never seen a diabetes educator or a dietitian. He was checking his glucose levels 4 times a day. He was smoking half a pack of cigarettes a day. On examination, his weight was 132 kg (BMI 39.5); blood pressure 145/71; and signs of mild peripheral neuropathy were present. Laboratory tests noted an HbA1c value of 8.1%, urine albumin 3007 mg/g creatinine (normal <30), serum creatinine 0.86 mg/dL (0.61–1.24), total cholesterol 128 mg/dL, triglycerides 86 mg/dL, HDL cholesterol 38 mg/dL, and LDL cholesterol 73 mg/dL (on atorvastatin 40 mg daily). How would you treat this patient?
The endocrine pancreas in the adult human consists of approximately 1 million islets of Langerhans interspersed throughout the pancreatic gland. Within the islets, at least five hormone-producing cells are present (Table 41–1). Their hormone products include insulin, the storage and anabolic hormone of the body; islet amyloid polypeptide (IAPP, or amylin), which modulates appetite, gastric emptying, and glucagon and insulin secretion; glucagon, the hyperglycemic factor that mobilizes glycogen stores; somatostatin, a universal inhibitor of secretory cells; pancreatic peptide, a small protein that facilitates digestive processes by a mechanism not yet clarified; and ghrelin, a peptide known to increase pituitary growth hormone release.
TABLE 41–1Pancreatic islet cells and their secretory products. |Favorite Table|Download (.pdf) TABLE 41–1 Pancreatic islet cells and their secretory products.
|Cell Types1 ||Approximate Percent of Islet Mass ||Secretory Products |
|Alpha (A) cell ||20 ||Glucagon, proglucagon |
|Beta (B) cell ||75 ||Insulin, C-peptide, proinsulin, amylin |
|Delta (D) cell ||3–5 ||Somatostatin |
|Epsilon cell ||<1 ||Ghrelin |
Insulin is a small protein with a molecular weight in humans of 5808. It contains 51 amino acids arranged in two chains (A and B) linked by disulfide bridges; there are species differences in the amino acids of both chains. Proinsulin, a long single-chain protein molecule, is processed within the Golgi apparatus of beta cells and packaged into granules, where it is hydrolyzed into insulin and a residual connecting segment called C-peptide by removal of four amino acids (Figure 41–1).
Structure of human proinsulin (C-peptide plus A and B chains) ...