A variety of platelet functional disorders in vitro has been reported in diabetes mellitus.
Plasma β-thromboglobulin (β-TG) and platelet factor 4 (PF4) levels have been assumed to reflect the in vivo platelet release reaction. However, these two proteins display different physical and biological properties.
We studied the plasma β-TG and PF4 levels in diabetes mellitus using radioimmunoassay kits.
The results showed that plasma β-TG and PF4 levels were significantly elevated in poorly controlled diabetics independently of vascular complications, and the degree of elevation of β-TG levels was not correlated with the severity of diabetic retinopathy.
The concentration of plasma β-TG was correlated with the concentration of serum creatinine, but the concentration of plasma PF4 was not. These results indicated that the concentration of plasma β-TG does not accurately reflect the in vivo platelet release reaction in renal insufficiency. However, raised β-TG and PF4 levels in poorly controlled diabetics without renal insufficiency may provide support for platelet activation and hypercoagulable statec

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Determinations were made of the C-peptide immunoreactivity (CPR) and ¹²⁵I-insulin antibody binding percent in the serum of venous blood from 11 insulin-treated pregnant diabetics and from the umbilical cord of their newborns.
At delivery, the maternal and cord CPR levels for the pregnant diabetics were 2.3±1.9 and 4.6±2.9 ng/ml (mean ± SD), respectively. In contract, the maternal and cord CPR levels in 12 normal pregnants were found to be 3.2±1.7 and 1.5±0.3 ng/ml, respectively. The cord CPR levels of the offspring of diabetic mothers were thus significantly higher than those in normal subjects (p<0.01).
Three newborns from among the 11 diabetic mothers had associated hypoglycemia with below 30mg/dl of blood glucose. Another newborn with 35 mg/dl of blood sugar suffered from convulsions, and it was considered that these symptoms were caused by the hypoglycemia. High CPR levels were found in the cord serum of the 4 above newborns, with a mean CPR level of 7.5±3.0 ng/ml. This was significantly higher the mean of 3.0±1.2 ng/ml for those without hypoglycemia (p<0.01).
No significant differences were noted between the maternal and cord ¹²⁵I-insulin antibody binding percent, and there was no positive correlation between cord CPR levels and maternal ¹²⁵I-insulin binding percent.
It was found by gel chromatography that a high CPR was composed of both proinsulin and Cpeptide.
It is suggested that fetal hyperinsulinism may cause hypoglycemia in newborns of diabetic mothers.

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The concentrations of fast minor components of hemoglobin (Hb), designated as glycosylated hemoglobin or hemoglobin AI, are elevated in diabetic patients. Furthermore, it has been reported that glycosylated Hb measurements form a good index of long-term blood glucose control in diabetic patients.
In the present study, investigations were made of the formation of fast Hb by means of various drugs without glucose, and on the physiological actions.
Fast Hb was measured by ion-exchange column chromatography using the modified Trivelli's method, and high performance liquid chromatography was employed for the separation of fast Hb fractions. The formation of fast Hb based on incubation of red blood cells with ascorbic acid, glyceraldehyde, pyridoxal HC1 and other aldehyde compounds, was observed.
Such fast Hb were produced in short-term and large quantities when compared with the fast Hb formed by glucose.
Oxygen dissociation curves (ODC) for the red blood cells containing the fast Hb formed by incubation with pyridoxal HC1 or glyceraldehyde as representative aldehyde compounds for 3 hours at 37°C, were determined with a “HEM-O-SCAN” oxygen dissociation analyzer (AMINCO, Inc). With these fast Hb, the ODC shift was shown on the left.
The above results suggest that the oxygen affinity was increased by such fast Hb. Furthermore, the fast Hb formed by glucose were followed by an increase in the HbAic fraction, and the fast Hb formed by aldehyde compounds in vitro contained increased amounts of not only the HbAic, but also the HbAr a+b fraction.

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The total protein (TP) concentrations in the cerebrospinal fluid (CSF) and the protein fractions analyzed by disc electrophoresis were evaluated in 54 diabetic patients (27 males and 27 females; average age 47) and 12 normal controls (6 males and 6 females; average age 42). The diabetic complications were classified into neuropathy, retinopathy, nephropathy, and microangiopathy (retinopathy and/or nephropathy).
The mean TP concentration in normals was 26±2mg/dl (mean±SEM). In 23 diabetics without any type of complications, it was 33±2mg/dl, which was significantly higher than the value for the normals (p<0.05) but still within the normal range (mean±2 SD of normals). The concentration in 31 diabetics with complication (s) was 54±7mg/dl, which was significantly higher than the value for the diabetics without complications (p<0.01).
A significant correlation was observed between the TP concentrations and the severity of diabetic retinopathy based on Scott's classification (p<0.01). The levels of TP in diabetics with only neuropathy (n=12) were within the normal range, and those in diabetics with microangiopathy alone (n=3) were significantly elevated. No definite correlation was observed between the levels of average fasting blood glucose over 2 weeks prior to CSF collection and the TP concentrations in the CSF of diabetics.
The densitometric tracing patterns of disc electrophoretograms of CSF proteins revealed 8 fractions: prealbumin (PrA), albumin (A), α-lipoprotein (α-LP), α'-globulin (α'-G), transferrin (Tr), β'-globulin (β'-G), γ'-globulin (γ'-G), and slow α₂-globulin (sα₂-G). The concentrations of the A, α-LP, α'-G, Tr, γ'-G, and sα₂-G fractions were significantly increased in diabetics with complication (s) and were significantly correlated with the severity of diabetic retinopathy. In diabetics with microangiopathy, elevated concentrations of A, α'-G, Tr, γ'-G, and sα₂-G were observed and markedly high levels of Tr and sα₂-G were noticed in diabetics with microangiopathy alone. It was apparent therefore that the elevation of concentrations of the above protein fractions might contribute to the increased TP concentrations in the CSF of diabetics.
The above results suggest that elevated TP concentrations of the CSF in diabetics might occur under the strong influence of diabetic microangiopathy rather than neuropathy, and that the most common pattern in the disc electrophoretograms of CSF total proteins in diabetics with mi croangiopathy is elevated sα₂-G fraction protein.

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Since there have been few reports on amenorrhea in patients with diabetes mellitus, we describe the prevalence of amenorrhea and its clinical findings in patients with diabetes mellitus investigated retrospectively at our clinic, the Diabetes Center of Tokyo Women's Medical College.
Investigations were performed on 203 premenopausal women with diabetes mellitus who had visited our clinic between May 1966 and December 1977. In 31 of them (15.3%), amenorrhea was observed. The prevalence of amenorrhea was significantly higher in the group with diabetes mellitus than in the normal healthy control group (6.4%, 8 of 125 patients) and in the control group with other diseases (7.4%, 13 of 176 patients).
Amenorrhea occurs more frequently in young people who have just suffered from diabetes mellitus.
Aggravation of abnormal metabolism such as development of diabetes mellitus, diabetic coma and inappropriate control of diabetes mellitus was observed to be an inducing factor of amenorrhea.
However, recovery from the amenorrhea was not related to the control of blood glucose.
In order to investigate the causes of amenorrhea, LH-RH tests were performed and the plasma level of total estrogen was determined in some of our diabetic patients. The LH-RH test was performed in 21 premenopausal women with diabetes mellitus who were chosen from outpatients of the Diabetes Center, Tokyo Women's Medical College, and in 16 subjects among them the plasma estrogen level was determined. The LH-RH test in the diabetic group revealed a lower response to LH than in the normal contrl group. However, there was no difference in responses to LH and FSH between the diabetic states of good and fair control. The response to LH was strikingly decreased in diabetics with ameno rrhea. Two patients in whom the LH-RH test was performed before and after recovery from amenorrhea revealed lower responses to LH and FSH at the time of amenorrhea than at the time of normomenorrhea.The plasma total estrogen showed lower levels in diabetics with amenorrhea (6 cases) than in normal subjects (15cases).

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An attempt was made to establish a normal range of serum IRI levels during the 50 g oral glucose tolerance tets (OGTT). Since it is well known that serum IRI levels tend to be largely heterogeneous, it is most important to select appropriate subjects for obtaining an improved estimate of normal values, excluding those factors which might lead to variations in the IRI levels. In the present study, 236 healthy people who were admitted for health examinations and were confirmed to have normal glucose tolerance, no obesity and no family history of diabetes, were selected.
(1) The subjects were subdivided into two groups. One had none of the.following findings; hypertension, arteriosclerosis, hepatic dysfunction or impaired lipid metabolism (112 cases). The other group had one or more of those findings (124 cases). The serum IRI levels of the two groups, were compared, and it was found that the variance, a parameter indicating the dispersion of distribution, was significantly less in the group without the findings (the so-called “normal group”) than in the other group, indicating a far lower dispersion in the normal group.
(2) The relation between serum IRI levels and age and sex was examined. Partial correlation analysis gave no significant correlation coefficients between five IRI measurements (from fasting to 120 min) and sex or age, except in the case of one measurement, the 60-min value, suggesting no strong effect of age or sex on the serum IRI levels. (3) In the normal group, the fasting IRI level was distributed within a vary limited range, but at 30 min and 60 min after glucose loading, the levels were dispersed over an extremely wide range. However, the 120 min value already showed a tendency to converage, and the 180-min value was again within the original narrow distribution.
(4) The means and standard deviations of the serum IRI levels during the OGTT were estimated by the normal probability paper method (Hoffman's method). The results obtained were 7.5±2.9, 39.0±16.0, 36.0±13.5, 14.0±6.4 and 7.4±3.0 (μU/ml) for the fasting, 30-min, 60-min, 120-min, and 180-min levels, respectively.

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The endocrine and exocrine function as well as histological changes in the pancreas were examined in dogs after partial ligation of the pancreatic duct.
The 7beta;-cell function of the islets was progressively depressed and insulin deficiency was observed after 4 months of partial ligation, whereas there was only a minor decline in α-cell function.
Such damage to pancreatic endocrine function was more severe in cases with advanced fibrosis than in cases with minimum fibrosis, as induced by partial pancreatic duct ligation.
The exocrine function of the pancreas began to decline within 1 month after ligation, and was almost completely abolished after 3 months.
Such experimental chronic pancreatitis did not affect the liver function or serum lipid levels.

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Almost all symptoms of diabetic gangrene have so far been noted in the lower extremities. Their occurrence in the upper extremities is reported to be very rare. Recently, however, we treated one diabetic patient who had a spot of gangrene in the finger.
The patient, a 50-year-old male, has suffered from diabetes for the last 7 years. He has been treated with oral hypoglycemic agents for the last 2 years, since.July 1977. In August, 1977, when gangrene first occurred, he was injured slightly in the fourth toe of the left foot, but it was soon cured. A year later, in August, 1978, a rose thorn pierced and entered the tip of the fourth finger of the right hand, and gangrene again appeared. Angiography revealed complete obstruction at the ulnar artery, with blood flow to the fourth and fifth fingers supplied by collateral flow through the interosseous and radial arteries.
Burger's disease was suspected because of the patient's smoking history, the regions in which the symptoms occurred, and rather deficient angiographic findings for atherosclerotic lesions. However, there was a background of diabetic microangiopathy and neuropathy, and the patient was diagnosed as diabetic gangrene based on the manner of cure and reduction of pain through the use of insulin, although the patient continued smoking, and the fact that the gangrene had been triggered by a wound, and spot-like findings were obtained by thermography.
A switch was made from oral hypoglycemic agents to insulin injection, performed in combination with local insulin pack therapy. Antibiotics and peripheral vasodilators were also administered concomitantly. About 6 months later, in January, 1979, the gangrene was cured, and no relapse had occurred as of June, 1979.

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