Serum cholesterol 220 mg/dL <200 mg/dLLAB 10: DIABETES CASE CONFERENCEObjectives: By the end of this lab session, you should: 1. Understand insulin-dependent diabetes (IDDM) 2. Understand what is currently known about non-insulin dependent diabetes (NIDDM) 3. Understand the general mechanism by which insulin results in increased glucose uptake3. Understand the role of insulin in controlling carbohydrate and lipid metabolism4. Understand the basis for the metabolic acidosis and ketosis associated with IDDMCASE 1: INSULIN-DEPENDENT DIABETESHISTORY:Tyler F, a 17-year old high school student, was brought to the emergency room in a coma. His mother said that her 6' 2", 175-pound son was physically active, and was a starting tight end on the high school football team. However, during the past month, he had lost 12 pounds. She also had noticed that he was excessively thirsty, drinking larger than normal quantities of Gatorade and fruit juices. Tyler also urinated voluminously, voiding several times during the night. The admitting physician immediately drew a blood sample and ordered blood gas and other analyses. A urine sample was also obtained and analyzed with a Multistix dipstick. The results of the urinalysis showed a 5+ reaction for glucose (=1000-2000 mg/dL), a 4+ reaction for ketone bodies (=80 mg/dL), and a specific gravity of 1.030 (normal range = 1.003 - 1.030). Results of a physical examination were basically negative, except for moderate hyperventilation.LABORATORY DATAPatient Normal RangeArterial blood gases tests (upon admission)pH 7.23 7.35 - 7.45pCO230 mm Hg 35-45 mm HgHCO3–12 mEq/L 22-26 mEq/LSerum glucose 1100 mg/dL 65-120 mg/dLSerum Osmolality (~ specific gravity) 440 mOsm/kg 275-300 mOsm/kgSerum lactate dehydrogenase (LD) 121 U/mL 100-150 U/mLSerum AST (liver marker) 24 U/mL 8-30 U/mLSerum ALT (liver marker) 35 U/mL 10-50 U/mLSerum bilirubin (Hb breakdown marker) 1.1 mg dL 0.2-1.2 mg/dLThe symptoms and lab data were what would be expected for hyperglycemic ketoacidosis associated with diabetes mellitus. The blood gas analyses on admission were consistent with metabolic acidosis with partial respiratory compensation. Upon further discussion with the mother, it was learned that twoof her brothers and several uncles were diagnosed as having diabetes. The patient was treated in the emergency room with intravenous insulin and intravenous fluids, and he was admitted to the hospital. Later test results during hospitalization are shown below.Patient Normal RangeSerum glucose tests (post-admission)Fasting 250 mg/dL 70-115 mg/dL2-hour post-prandial 500 mg/dL <140 mg/dLOral glucose tolerance testFasting 150 mg/dL 70-115 mg/dL30 minutes 300 mg/dL <200 mg/dL1 hour 325 mg/dL <200 mg/dL2 hours 390 mg/dL <140 mg/dL3 hours 300 mg/dL 70-115 mg/dL4 hours 260 mg/dL 70-115 mg/dLGlycosylated hemoglobin 9% 2.2 - 4.8%During the first 72 hours of hospitalization, the patient was monitored by frequent serum glucose determinations, and insulin was administered according to the results of these tests. The patient's condition was eventually stabilized with 40 units of neutral protamine Hagedorn insulin/day. The patientwas given comprehensive instruction on self-blood glucose monitoring, insulin administration, diet, exercise, and recognition of signs and symptoms of hypoglycemia and hyperglycemia, and he was discharged one week after admission.CASE 2: NON-INSULIN DEPENDENT DIABETESHISTORY:Donnatella C., a 28-year old mother of 2 children, applied for a new life insurance policy after her husband died. She truthfully told the insurance company that she had an elevated serum glucose concentration during her second pregnancy, and that her 58-year old mother had developed kidney failure after a 20-year history of non-insulin-dependent diabetes mellitus (NIDDM). Donnatella was told be the insurance company that she was not insurable because she had a "pre-existing condition", namely, diabetes.Donnatella visited her physician, who performed a physical examination. The results of the exam were in the normal range, except for a calculated body-mass index (BMI) of 30. The BMI relates a person’s weight to their height and compares the value with the value for the population at large. A BMI of 30 indicates that Donnatella is somewhat overweight for her height. The following laboratory tests were also obtained:Patient Normal RangeUrine glucose trace negativeUrine protein negative negativeFasting plasma glucose 139 mg/dL < 140 mg/dL2hr post-prandial glucose 185 mg/dL <200 mg/dLglycosylated hemoglobin 4.8% 2.2 - 4.8%Serum cholesterol 220 mg/dL <200 mg/dLBreakfast: coff ee + cream/ sugarMid- AM: coff ee + cream/ sugarapple danishLunch: Tuna salad sandwich w/ mayonnaisesmall salad w/ oil/ vinegar dressing4 large chocolate chip cookies16 oz Pepsi-ColaAfternoon: Doritos Cool-Ranch chips16 oz Pepsi-ColaSupper: 12 Triscuits (eaten while cooking)2 pork chops, f ried½ cup applesauce1 cup mashed potatoes w/ 1 T but ter1 cup green beans w/ 1 T but ter1 slice apple pie w/ 1 scoop vanilla ice creamsweet teaTV snacks: Mesquite-smoked BBQ potato chips16 oz Pepsi-ColaThe physician ordered an oral glucose tolerance test. After an overnight fast, a baseline blood sample was drawn for both glucose and insulin levels. Then Donnatella drank 100 grams of glucose and blood samples were drawn after 0.5, 1, 2, and 3 hours. The results of her tests are shown below.The shaded areas in the graphs indicate the normal range of expected values. This range is usually the 95% confidence interval, i.e., it includes 95% of the values from a healthy population. Donnatella's physician also sent her to a clinical dietitian for an analysis of her diet. He recorded the following data for a typical day with Donnatella:BACKGROUNDHormones play vital roles in the overall integration of metabolism. Insulin and glucagon, in particular, have marked effects on the uptake, storage, and mobilization of fuels, and on related aspects of metabolism. Insulin is secreted by the -cells of the pancreas in response toelevated plasma glucose. Insulin is a peptide hormone thatconsists of two chains - an A chain of 21 amino acids and a Bchain of 30 amino acids - that are covalently joined by twodisulfide bonds. Insulin is synthesized as a single precursorprotein, preproinsulin, that contains about 55 amino acids notpresent in the mature insulin molecule (see Figure below).