Eiichi Ubukata

Diurnal Variation of Blood Ketone Bodies in Insulin-Dependent Diabetes mellitus and Noninsulin-Dependent Diabetes mellitus Patients: The Relationship to Serum C-Peptide Immunoreactivity and Free Insulin

We examined whether the rise in ketone body concentration around midnight and in the early morning was due to the lack of free insulin (IRI) or excess of insulin counterregulatory hormones such as human growth hormone (hGH), cortisol and glucagon in noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) patients and whether the monitoring of blood ketone body concentration was clinically useful as an index of metabolic control for deciding to increase or decrease the insulin dose in the treatment of diabetes mellitus. Serum levels of 3-hydroxybutyrate (3-OHBA), acetoacetate (AcAc) and 3-OHBA/AcAc ratio before breakfast were significantly increased in insulin-treated NIDDM patients with well-controlled fasting plasma glucose levels and IDDM patients compared to those in normal subjects. Mirror image diurnal changes were found between serum concentrations of 3-OHBA and serum C-peptide or free IRI in normal subjects and NIDDM patients treated with diet alone or sulfonylurea during the 24-hour daily profiles. However, there were no correlations between 3-OHBA and free IRI in the NIDDM patients treated with insulin and IDDM patients who had a much larger increase in the mean concentration of serum 3-OHBA at 6 a.m. caused by a low concentration of free IRI. Counterregulatory hormones were not increased in IDDM patients compared to normal subjects in the early morning. Cortisol/free IRI and hGH/free IRI molar ratios were significantly increased in NIDDM and IDDM patients compared to normal subjects in the early morning, but glucagon/free IRI molar ratio was not changed between IDDM and normal subjects. In conclusion, the early morning rising of ketone body concentration in insulin-treated diabetic patients, particularly IDDM patients, is due to the absolute lack of free IRI and/or the relative lack of free IRI to the levels of hGH or cortisol, and the monitoring of 3-OHBA is clinically useful as a more sensitive index of metabolic control.

Effect of various glucagon/insulin molar ratios on blood ketone body levels in rats by use of osmotic minipumps

The bihormonal control by insulin and glucagon of blood ketone body level was studied. Mixed solutions with various molar ratios of glucagon and insulin (G/I) were subcutaneously infused continuously for five days by use of the osmotic minipump in the normal rats. The concentrations of insulin and glucagon solution were set at the high G/I molar ratio, the moderate G/I molar ratio and the low G/I molar ratio. In addition, the moderate G/I molar ratio group was divided into three sub-groups: low glucagon and low insulin, moderate glucagon and moderate insulin, and high glucagon and high insulin. After five days, the rats were decapitated to measure plasma ketone body, free fatty acid (FFA), glucose, insulin and glucagon. The FFA level was not significantly different among three groups. The glucose level was not different between the high and moderate G/I molar ratio groups, and decreased in the low G/I molar ratio group. 3-beta-hydroxybutyrate (3-OHBA) and acetoacetate (AcAc) levels in the high G/I molar ratio group were elevated, and 3-OHBA level in the low G/I molar ratio group was lowered compared to those in the moderate G/I molar ratio group. Among three moderate G/I molar ratio sub-groups, there was no difference in 3-OHBA and AcAc levels. These results demonstrate that plasma ketone body levels are controlled by the plasma G/I molar ratio.

A Pentamidine-Treated Acquired Immunodeficiency Syndrome Patient Associated With Sudden Onset Diabetes mellitus and High Tumor Necrosis Factor α Level

INTRODUCTION found on his back. The hemoglobin level was 13.8 g/ dL, leukocyte count was 392/mL, and no abnormal About 60% of patients with acquired immunodeparameters of the renal and liver functions were found ficiency syndrome (AIDS) develop phenuexcept for 840 IU (normal, 140–360 IU) of lactic dehymocystis pneumonia.1 The present drugs drogenase (LDH). In addition, Human Immunodefiof choice include sulfamethoxazole/triciency Virus (HIV) antibodies were found, and the methoprim and pentamidine. Pentamidine-induced CD4/CD8 lymphocyte ratio was 0.05 (CD4 8 cells/mL, diabetes mellitus is a serious side effect. Plasma tumor CD8 165 cells/mL). On breathing room air, the patient necrosis factor a (TNF-a) increases in some AIDS pashowed severe hypoxemia (PaO2 46.5 Torr) with low tients.2 TNF-a is associated with the insulin resistance3 PaCO2 (27.2 Torr). Chest X-ray revealed bilateral difand pancreatic b cell dysfunction.4 We report one pafuse alveolar infiltrates. A bronchoalveolar lavage was tient with a very high level of plasma TNF-a who performed on hospital day 1, and the sample demonacquired diabetes mellitus following pentamidine strated the presence of Pneumocystis carini (silver treatment for pneumocystis pneumoniae. stain). He was treated with intravenous pentamidine isethionate 150 mg/day (3 mg/kg) and peroral sulfamethoxazole/trimethoprim (8 g/day). On hospital day CASE REPORT 11, plasma glucose was 80 mg/dL after breakfast. On A 29-year-old heterosexual man with a 4-week history hospital day 30, he had complaints of thirst, polydipsia, of fever, dyspnea, and productive cough was admitted and polyuria. Fasting plasma glucose was 1440 mg/ to our hospital. He had no previous history of any dl. Other laboratory data in this point showed urinary serious disease and no family member with diabetes glucose 41, urinary ketone 1, serum insulin 6 mU/ mellitus. He was found to have fever (37.48C), tachycarmL, serum C-peptide 1.5 ng/mL, serum ICA antibody dia (90 beats/min), tachypnea (30 breaths/min), and negative, serum GAD antibody negative, TNF-a 220 cyanosis. Chest auscultation revealed Velcro rales in pg/mL (normal LT 6) and IL-6 44 pg/mL (normal LT the bilateral lower lung area. Kaposi’s sarcoma was 25). The treatment of sulfamethoxazole/trimethoprim and pentamidine isethionate was discontinued. The patient received intravenous fluid hydration and regu-