It has been shown that in diabetic patients, peripheral nerve function is retained during ischemia longer than in normal subjects, indicating some resistance to ischemia. The purpose of the present study was to investigate the mixed nerve function of the median nerve before, during and after 30 min of ischemia, and to evaluate the relations between changes in peripheral nerve function during ischemia and other manifestations of diabetes.
Forty-three diabetics and 9 normal subjects were examined. In order to produce ischemia, a pneumatic cuff was applied around the upper arm, and the pressure was raised to at least 60 mmHg above systolic pressure. Median nerve action potentials (NAP) were evoked by electrical stimulation at the wrist and were recorded with surface electrodes at the elbow every minute during and after the 30min of induced ischemia.
Normal subjects complained of paresthesia soon after the beginning of ischemia, followed by hypesthesia and anesthesia. The amplitudes of the NAP decreased rapidly and disappeared within 18 to 20 min after the beginning of pressure application. On the other hand, ischemia-induced paresthesia and hypesthesia were remarkably reduced in all diabetics. The preischemic amplitudes of the NAP were smaller than those in normal subjects (p<0.005). However, the potential amplitudes during ischemia decreased more slowly than in the controls (after 15 min of ischemia; p<0.001). The disappearance time of NAP during ischemia was longer than 22 min in all diabetics. In only 6 patients, the disappearance time was between 23 and 29 min. The amplitudes of the NAP in the remaining 37 diabetics (86.0%) persisted even after 30 min. This phenomenon was observed in diabetics with no clinical findings or slowing in the nerve conduction studies suggestive of diabetic neuropathy, and was also observed in diabetics with a diabetic history of less than 1 year including 3 patients with IDDM. The amplitudes of the NAP after 15 and 30 min, and the disappearance time of NAP correlated significantly with the HbA1c and HbA1 levels. In addition, the disappearance time of NAP during ischemia improved in patients in optimal glucose control after diet alone or combined with insulin therapy.
It was concluded that the abnormal resistance to ischemia in diabetics could represent one of the earliest manifestations of peripheral nerve dysfunction prior to the appearance of clinical abnormalities and slowed nerve conduction, and might be affected by metabolic defects. The present method is simple and readily available. For its routine clinical use, at least 15 min of ischemia is sufficient to distinguish diabetics from normal subjects.

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Computed tomography (CT) of the pancreas usually shows either a smooth or granular image in the margin and contents, We have divided these images into three types in boththe margin and contents (smooth type, fine-granule type and rough-granule type). These typeswere analyzed in relation to the clinical features of diabetes mellitus. Four hundred and six controls without diabete, mellitus, gallstones, pancreatitis, liver cirrhosis or malignant tumors were analyzed as a control group, and 121 diabetic patients without these four complications were analyzed as a diabetic group. The following results were obtained.
1. In the control group, the younger obese persons showeds high incidence of the rough-granule type of the pancreatic margin and contents. This decreased with an increase in age.
2. In the diabetic group, the incidence of the rough-granule type of both the pancreatic margin and contents was high among the elderly and older patients. Lean patients did notshow the roughgranule type of pancreatic contents. The incidence of the rough-granule type tended to decrease as the clinical features became worse.
3. Pancreata having the rough-granule type of pancreatic contents were consideredto be rich in fat tissue.

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The correlations between arteriosclerosis and 18 clinical and laboratory findingswere studied in 96 non-insulin dependent diabetics (mean age 60. 1 years) and 44 non-diabetics (mean age 64.9 years) by multivariate analysis. The evaluation of macroangiopathy was examined by ST changes in ECG (ST-ECG), aortic pulse wave velocity (APWV) and aortic arc calcification (AAC). The 18 clinical and laboratory findings were age, sex, weight index, presence of diabetes, duration of diabetes, kinds of therapy, total cholesterol (TC), HDL-cholesterol (HDL-C), triglyceride (TG), creatinine, control of blood glucose, presence of albuminuria, presence of hypertension, blood pressure at APWV and ECG examinations, and presence of anamnesis of myocardial infarction, angina pectoris and cerebrovascular accidents.
1) The factor of diabetes (except for the other factors associated with diabetes) was not correlated with ST-ECG, APWV or AAC.
2) The degree of ST-ECG findings was closely and positively related to age and duration and negatively related to HDL-C. ST segment depression (ST-ECG) in females was greater than in males.
3) APWV in diabetics undergoing insulin therapy was faster than in those being treated with oral hypoglycemic agents or diet therapy. The velocity was positively related to the levels of blood glucose, TG and albuminuria.
4) AAC was closely and positively correlated with age. AAC was unrelated to kinds of therapy, duration, control of blood glucose, HDL-C or TG.

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Exocrine pancreatic function assessed by an oral BT-PABA load (PFD test) was investigated in 58 diabetics with special reference to endogenous insulin response to oral glucose stimulation.
1. PABA urinary recovery was correlated with the parameters of maximal bicarbonate concentration in the pancreatic juice, volume of pancreatic juice and amylase output following pancreozymin and secretin injections (P-S test).
2. PABA urinary recovery in diabetics was 69.0±2.4%(mean±S.E.), which was significantly lower than the normal value of 84.8±1.3% in 21 control subjects.
3. PABA urinary recovery in diabetics was correlated with the serum pancreatic isoamylase activity.
4. The decrease of PABA urinary recovery in diabetcs was particularly pronounced in those with prolonged duration of diabetes, a high level of fasting blood glucose and those with no detectable IRI response to oral glucose stimulation.
Therefore, exocrine pancreatic dysfunction in diabetics was closely related to the lack of endogenous insulin secretion.

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Various autonomic function tests were performed before and after intravenous administration of atropine to determine whether the parasympathetic nerves were damaged earlier than the cardiac sympathetic nerves in the reflex control of heart rate in diabetics.
Fifteen diabetic patients without symptoms of autonomic neuropathy (DM group, 49±9 years) and 9 healthy subjects (N group, 44±10 years) were studied. The autonomic function tests included the baroreceptor sensitivity (BS), Valsalva ratio (VR), beat-to-beat variation in heart rate with deep respiration (DR), and heart rate response to sustained handgrip (HG) and 60° passive tilt (Tilt).
BS and DR were abolished by atropine in both groups. However, HG and Tilt were partially decreased by atropine (48% and 71% respectively). Before atropine, BS, DR and VR were each significantly lower in the DM group than the N group (p<0.01, p<0.001, and p<0.01 respectively), but HG and Tilt were not significantly different between both groups. After atropine, each test showed no significant difference between the groups.
These results suggest that the parasympathetic nerves are affected earlier than the cardiac sympathetic nerves.

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In order to analyze the role of obesity in the pathogenesis of diabetes, the maximal weight index in the past was investigated in about 800 patients with non-insulin-dependent diabetes (NIDDM) and 56 patients with insulin-dependent diabetes (IDDM). The maximal weight index (MWI) was calculated from the maximal previous body weight obtained by inquiry and the present body height. Family history was also taken by interview. The first occurrence of diabetic symptoms or detectionof urine glucose was taken as the onset of diabetes.
In IDDM, the MWI was +5.7±13.6% in males and +15.0±14.9% in females and 57% showed less than +10% of the standard body weight. The MWI exceeded +20% in 17% of the males and in 30% of the females. These obese patients were more frequently seen among those with the onset of diabetes at more than the age of 30.
In NIDDM, the MWI was similar in the males (+28.8±18.1%) and females (+30.9±20.7%). The frequencies of obese patients (MWI≥+20%) and very obese patients (MWI≥. +40%) were 68% and 29%, respectively, but 15% of patients had never been obese at all in the past (MWI<+10%). The mean MWI was lower in groups with the onset of diabetes at younger ages (e. g., MWI values of groups with the onset of diabetes at less than 30 and in their 40s and 60s were +26.1, +29.3 and 31.5% respectively).
NIDDM patients were then classified into three groups according to their MWI. In patients who developed diabetes before the age of 30, 48% belonged to the non-obese group (MWI<+20) and 28% to the moderately obese group (MWI: +20-39%), while in patients with the onset of diabetes at more than 40, the percentage of moderately obese patients increased from these data, the occurrence of NIDDM developing in middle age seemed to be associated with a gain of body weight during this period.
In patients who had diabetic parents, the MWI was significantly lower than in those without diabetic parents (+ 23.9±17.8% vs +31.3±19.4%, p<0.001). There was no significant difference between MWI values of patients with and without diabetic siblings.
These results confirmed a high prevalence of past obesity among NIDDM patients as compared to IDDM patients. On the other hand, it was also shown that IDDM patients with the onset of diabetes after the age of 30 often had previous obesity. A significant portion of NIDDM patients had never been obese previously and the lean NIDDM patient was more prevalent in the youngonset group. The MWI was lower in NIDDM patients with diabetic parents than in those without diabetic parents. It is suggested that obesity acts as a diabetogenic factor in the occurrence of NIDDM, especially in patients with the onset at older ages and with a lesser degree of hereditary loading of diabetes.

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Physical training has been shown to have beneficial effects. The purpose of the present study was to estimate training effects quantitatively. The tissue sensitivity to exogenous insulin was evaluated in 8 trained athletes and 11 untrained controls. Insulin sensitivity was determined by the euglycemic insulin clamp technique (insulin infusion plus a variable glucoseinfusion). The amount of glucose infused is a measure of the overall tissue sensitivity to insulin.
During the insulin clamp study, comparable plasma glucose (80-90mg/dl) and insulin (70-100μU/ml) levels were achieved in both groups. However, the glucose infusion rate in the athletes (11.14±0.48mg/kg/min) was significantly higher than in the controls (7.48±0.23mg/kg/min)(p<0.001). After physical training for 1 month, the glucose metabolism in the controls increased from 7.75±0.21mg/kg/min to 8.60±0.99mg/kg/min (p<0.05). During euglycemic hyperinsulinemia, both FFA (p<0.01) and glycerol (p<0.001) decreased rapidly after physical training. Glucose metabolism was closely correlated with VO₂ max (r=0.7753, p<0.001).
It is concluded that the euglycemic insulin clamp technique provides a reliable estimate of training effects. The tissue sensitivity to physiological hyperinsulinemia is 47% higher in trained athletes, and physical training improves the insulin sensitivity not only in glucose metabolism but also in lipid metabolism. These results confirm that physical training can reduce the insulin requirement in insulin-dependent diabetics in addition to being beneficial to noninsulin-dependent diabetic patients.

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Myocardial lipoprotein lipase (LPL) activity in diabetes mellitus has not been fully established. The purpose of the present study was to compare two distinct fractions of myocardial LPL, a “functional” and “non-functional” type in isolated, perfused hearts from streptozotocin (STZ) induced diabetic rats.
The experimental diabetes was induced by injecting STZ (50 mg/kg) and the rats were sacrificed seven days later. The hearts were perfused for five minutes by the working heart mode with Krebs Henseleit bicarbonate (KHB) buffer. Then, the perfusate was switched to KHB buffer containing heparin (5μ/ml) and perfusion was continued for an additional 20 minutes. Coronary effluent was collected at five-minute intervals and assayed for functional LPL activity. At the end of perfusion, the heart was frozen by a Wollenberger clamp (-80°C) and lyophilized. It was homogenized in 0.05M ammonium buffer containing 0.5μ/ml of heparin and extracted to measure nonfunctional LPL activity.
The lipolytic activity of the perfusate had the characteristics of LPL, i.e. 1) lipase activity was stimulated by serum, 2) it was inhibited by 1M NaCl and protamine sulfate, and 3) the maximal lipolytic activity occurred at pH 8.6 when tested over a pH range of 3.0-9.2.
Functional LPL activities in the control rats were 406±46, 251±27, 132±27 and 76±23 nmoles FFA hydrolyzed/min at 5, 10, 15 and 20 minutes following the heparin administration, respectively. In the diabetic rats, these values were 307±55, 116±15, 80±21 and 54±28, which were significantly lower than in the control rats. On the contrary, non-functional LPL activity in the diabetic rats (77.2±10.9 nmoles FFA/min/whole tissue) was significantly higher than in the control rats (29.3±8).
From these results, it was suggested that there was a conversion defect from the precursor of LPL to the functional form of LPL in the hearts of the diabetic animals. Such a defect could be a consequence of insulin deficiency. Alternatively, since the plasma level of NEFA was higher in the diabetic than in the control rats and presumably the diabetic heart utilized circulating NEFA as the substrate rather than NEFA derived from LPL-mediated pathway, this high plasma NEFA could inhibit the conversion of the precursor form to the functional form of LPL.

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We report one case of acromegaly with diabetes mellitus, which was first diagnosed by diabetic ketoacidosis accompanied by acute pancreatitis.
The patient was a 32-year-old man. The presumptive age of onset of acromegaly was 25. In October 1982, he had abdominal pain and clouding of consciousness. Therefore, he was admitted to the emergency hospital. He was diagnosed as diabetic ketoacidosis. We suspected he had acute pancreatitis because the serum and urinary amylase were very high. Continuous intravenous insulin injection was started, and the maximum total daily insulin dose was 178 U. Subsequently, the control of blood glucose and his general condition were improved. The serum amylase diminished rapidly. The amylase creatinine clearance rate, lipase and elastase-I were still at a high level, but diminished slowly. Therefore, we suspected acute pancreatitis from the aspects of pancreatic function and morphologic examination. He was prescribed CB-154. In February 1983, he was treated by Hardy's operation and radiation. After the surgery and radiation therapy, the basal line of growth hormone and control of blood glucose were improved.
Secondary diabetes mellitus due to acromegaly is generally severe and insulin-resistant. Therefore, it is prone to diabetic ketoacidosis by infection or operation.

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We reported a case of diabetic ketoacidosis caused by predisposing to severe external otitis. We described the development of diabetic complications during 10 years in which the patient experienced five episodes of diabetic ketoacidosis after the onset of insulin-dependent diabetes.
A 22-year-old female was admitted because of severe pain in and discharge from the right external ear and diabetic coma. Her laboratory data showed the following values: pH 6.91, HCO₃^- 2 mEq/l, blood sugar 280 mg/dl, urinary ketone bodies 2+, HbAic 9.5%, 2, 3-DPG 0.364μmol/ml RBC. Culture from deep pus grew S. aureus. Low-dose intramuscular insulin injection (2 to 8U/h) and correction of dehydration ameliorated the diabetic coma. Considering the high level of HbAic and the low level of 2, 3-DPG, severe tissue hypoxia seemed to exist in this episode of diabetic ketoacidosis.
With regard to diabetic complications, cataracta and diabetic neuropathy appeared after the first episode of diabetic ketoacidosis in 1972. Diabetic retinopathy developed more rapidly than other complications after the other four episodes of diabetic ketoacidosis during 10 years. Thus, tissue hypoxia in diabetic ketoacidosis seems to play an important role in deteriorating diabetic retinopathy.

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In this paper, we demonstrated that short-acting human insulin (HI) loses solubility when mixed with intermediate-acting HI.
The recovery of soluble short-acting HI after having been mixed in varying ratios for different time periods with intermediate-acting HI was determined by radioimmunoassay.
When regular HI (recombinant DNA): HI (rDNA) and NPH·HI (rDNA) were mixed in a 1: 1 ratio and then immediately centrifuged, there was no significant loss of regular HI (rDNA), although there was a significant loss (-43%) in the 1: 3 ratio. In contrast, there was a large and a significant loss (-71%, -91%) of Actrapid semisynthetic HI (SHI) in the 1: 1 and 1: 3 ratios when mixed with Monotard SHI.
When regular HI (rDNA) and NPH·HI (rDNA) were mixed in 1: 1 and 1: 3 ratios after 20 min of incubation, there was a significant loss (-18%, -38%) of regular HI (rDNA). In contrast, there was a large and significant loss (-89%, -98%) of Actrapid SHI in the 1: 1 and 1: 3 ratios when mixed with Monotard SHI.
These changes may affect the clinical bioavailability of short-acting HI in HI mixtures.
Further studies are required to clarify the reasons for the mechanism of the loss of short-acting HI in HI mixtures.

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