Kazuo Takebe

Altered Postprandial Insulin Requirement in IDDM Patients With Gastroparesis

OBJECTIVE To evaluate the effect of gastric emptying on postprandial insulinrequirement in insulin-dependent diabetes mellitus (IDDM) patients with and without gastroparesis. RESEARCH DESIGN AND METHODS Postprandial insulin requirement and gastric emptying were simultaneously evaluated in five IDDM patients with gastroparesis and in six control IDDM patients without gastroparesis. Postprandial insulin requirement after test-meal intake was assessed by measuring the insulin infusion rate during a 4-h feedback control with an artificial endocrine pancreas device (Biostator, Life Science Instruments, Miles, Elkhart, IN). Gastric solid and liquid emptyings were evaluated during the Biostator study by measuring the disappearance rate of 99mTc in the stomach and in the time course of plasma acetaminophen concentration, respectively. RESULTS Total insulin requirement during the first 120 min after the test-meal intake was significantly lower in the gastroparetic patients than in the control patients. The gastroparetic patients showed no apparent postprandial peak for insulin infusion rate during the 4-h study, although the peak rate was observed within 120 min after the test-meal intake in the control patients. The disappearance of 99mTc in the stomach was significantly slower, and plasma acetaminophen concentrations were significantlylower in the gastroparetic patients compared with those in the control patients, respectively. CONCLUSIONS The results suggest that IDDM patients with gastroparesis, accompanied by impaired solid and liquid emptying, have an altered postprandial insulin requirement.

Erythromycin Derivative Improves Gastric Emptying and Insulin Requirement in Diabetic Patients With Gastroparesis

OBJECTIVE To evaluate the effect of the erythromycin derivative EM523L on gastric emptying and postprandial insulin requirement in insulin-dependent diabetic patients with severe gastroparesis. RESEARCH DESIGN AND METHODS In six IDDM patients with severe gastroparesis (two men and four women, mean age 44.5 years [range 36–53]), the insulin infusion pattern during feedback control with an artificial endocrine pancreas device (Biostator) after intake of a test meal, the retention rate of residual isotope (99mTc-labelled Sn-colloid) in the stomach, and the time-concentration curve of plasma acetaminophen as the marker for liquid emptying were studied with EM523L or a control placebo RESULTS Time courses of insulin infusion rates peaked within 120 min after intake of the test meal in the EM523L phase, whereas no apparent peak rates were observed in the control phase. The total amount of insulin required in the first 90 min postprandial was significantly greater in the EM523L phase than in the control phase. EM523L significantly decreased the residual isotope ratio in the stomach at ≥50 min postprandial and increased the plasma acetaminophen concentrations at 30–120 min postprandial, compared with respective values in the control phase. CONCLUSIONS Preliminary results obtained from a small number of patients suggest that EM523L or erythromycin analogs, which have agonistic activity to motilin receptors as well as no antibacterial effect, may be useful to accelerate gastric emptying and improve insulin requirement patterns, thereby establishing more stable glycemic control.

Correlation between bile acid malabsorption and pancreatic exocrine dysfunction in patients with chronic pancreatitis.

Fecal bile acid and fecal fat were determined in 18 normal subjects and 22 patients with chronic pancreatitis, and the relation of fecal bile acid excretion to exocrine pancreatic dysfunction was studied. In chronic pancreatitis fecal bile acid was approximately three times that of control subjects, and large amounts of primary bile acid were detected. A significant correlation between fecal bile acid excretion and bicarbonate secreted from the pancreas was found. This evidence of bile acid malabsorption was not observed until bicarbonate output was ∼0.05 mEq/h/kg. A slight correlation between fecal bile acid and absorption rates of fat was demonstrated. These results suggest that bile acid malabsorption observed in chronic pancreatitis is related to an impairment of pancreatic bicarbonate secretion.

Different change in lipoprotein(a) levels from lipid levels of other lipoproteins with improved glycemic control in patients with NIDDM.

OBJECTIVE To evaluate change both in lipoprotein(a) [Lp(a)] and lipid levels in other lipoproteins in non-insulin-dependent diabetes mellitus (NIDDM) after short-term improvement of glycemie control. RESEARCH DESIGN AND METHODS We compared Lp(a) levels in 210 NIDDM patients with those in 46 control subjects and evaluated the relationship between glycemie control and Lp(a) levels in diabetic patients. In addition, changes in Lp(a) levels and lipid levels were assessed after the improvement of glycemie control in 54 poorly controlled NIDDM patients. RESULTS In NIDDM, Lp(a) levels in all patients, 62 patients with HbA1c <6.0%, and 75 patients with HbA1c between 6.0 and 8.0%, were significantly higher than those in control subjects (19.1 [1.7-106.6], 19.2 [6.0-106.6], and 20.3 [2.7-75.3] vs. 15.4 [2.0-61.7] mg/dl, median [range], P < 0.05). Lp(a) levels in 73 patients with HbA1c of ≥8.0% (18.7 [1.7-58.8] mg/dl) were not significantly different from those in control subjects. After glycemie control, lipid levels in plasma and in other lipoproteins fell significantly, but Lp(a) did not change (from 18.3 [1.7-58.8] to 18.4 [6.6-95.3] mg/dl). Changes in lipid levels, including Lp(a), did not correlate with those in fasting plasma glucose or HbAlc. CONCLUSIONS These results suggest that elevated Lp(a) levels do not reflect poor glycemie control and that Lp(a) levels are independent of lipid levels in other lipoproteins after improved glycemie control in NIDDM.

Renal Effects of Bunazosin, a New αl-adrenoceptor Blocker, in Patientswith Mild-to-moderate Essential Hypertension

Renal effects of 4-week fixed maintenance doses of bunazosin three times daily (2.0 mg t.i.d., n = 8) and propranolol (40 mg t.i.d., n = 8) were evaluated in patients with mild-to-moderate essential hypertension [World Health Organization (WHO) stages I and II]. Both bunazosin and propranolol decreased blood pressure (BP) significantly (p < 0.05), but the magnitude of reduction in diastolic BP (DBP) was greater with bunazosin (p < 0.05) than with propranolol. Bunazosin produced a nonsignificant increase in renal blood flow (RBF) by 14%, a significant increase in glomerular filtration rate (GFR) 11% (p < 0.05), and a decrease in total renal vascular resistance (TRR) by 15% (p < 0.05), whereas propranolol caused no significant changes in these parameters. Urinary sodium excretion rate and the fractional excretion of sodium were unchanged by either of the drugs. The results of this shortterm study suggest that bunazosin may be a drug that will increase RBF and GFR and decrease TRR with a concomitant hypotensive action in patients with mildto-moderate essential hypertension. Whether these renal functional effects of the drug would benefit such patients must be determined in longterm studies.

Peripheral Lymphocyte Subset of Patients with Pancreatic Diabetes Mellitus

Patients with diabetes mellitus (DM) often suffer from various and severe infection. Patients with pancreatic DM have malnutrition due to chronic pancreatitis. Therefore it is believed that patients with pancreatic DM have a lower ability of host defence to infectious diseases than normal subjects. We examined the primpheral lymphocyte subsets (T cell, B cell, NK cell, CD3+ 56+ T) of eighteen patients (males, age = 52.8 +/- 12.7 years old, mean +/- SD) with pancreatic DM by two color flow-cytometry to evaluate the lymphocyte function. Ratios of T cell (T%, 66.9 +/- 9.3%, mean +/- SD). B cell (B%, 13.1 +/- 5.8%) and NK cell (Nk%, 19.3 +/- 8.7%) to total peripheral lymphocytes of patients with pancreatic DM were not significantly different from those (T% = 66.4 +/- 7.8%, B% = 13.5 +/- 6.7%, NK% = 19.9 +/- 9.1%) of thirteen normal subjects (males, age = 51.2 +/- 13.1). CD3+56+ T cell % (4.1 +/- 1.9%) of patients with pancreatic DM was lower than that (6.0 +/- 3.0%) of normal subjects (p < 0.05). CD3+56+ T cells have cytotoxic activity and it is likely that this activity is similar to that of NK cells. These results suggested that a decrease in peripheral CD3+56+ T cell % is a factor showing a weak host defense mechanism to infectious diseases in patients with pancreatic DM.

Idiopathic giant-cell granuloma of the pituitary with unusual clinical and histological features

A surgically treated idiopathic giant-cell granuloma of the pituitary in a 48-year-old man is described. Relative to previously reported cases, this case was unusual both clinically and histologically. Diabetes insipidus was the initial, and a prominent clinical, manifestation. Histological studies showed caseating granuloma or fibrosis in addition to a typical giant-cell granuloma. This is the first published documentation of the association of caseous necrosis in a patient diagnosed as having idiopathic giant-cell granuloma of the pituitary.Endocr Pathol 4:169–173, 1993.