bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin and Growth-Hormone Responses in Neonatal Hyperglycemia
Authors: Zarif Mehru , Pildes Rosita S , Vidyasagar D
Published: September 2013

Glucose, insulin, and growth hormone values were studied prospectively in 75 premature infants during the first five days after birth. Intravenous glucose was given at a mean rate of 4.7–4.9 mg./kg./in. (range 3–7). Mean birth weight was 1,394 α 47 gm. (mean α S.E.M.). Blood glucose values were significantly higher on days 1 and 2 than on days 3 to 5. Hypoglycemia (blood glucose <20 mg./100 ml.) occurred in two SGA and one AGA infants. On the other hand, hyperglycemia (>125 mg./100 ml.) was found in 32 of the 75 (42.7 per cent) infants. A significantly greater number of deaths occurred in infants with hyperglycemia (19/32) than in those with normoglycemia (19/32) than in those with normoglycemia (5/43). Mean plasma insulin values were significantly higher on days 1 and 2 (15 α 3 and 18 α 4 μU./ml.) than on days 3 and 4–5 (6 α 1 and 7 α 2 μU./ml.). In addition, mean insulin levels were significantly higher during hyperglycemic than during normoglycemic glucose levels at similar postnatal age. Growth hormone values were higher during the first three days than subsequently, but the values were similar in normoglycemic and hyperglycemic groups. Significant negative correlations were seen between glucose values on the first two days of postnatal life and birth weight, gestational age, and Apgar scores, whereas positive correlations were found with FiO2 and respiratory distress score (RDS).
Insulin and Free Fatty Acid Levels During Oral Glucose Tolerance Tests and Their Relation to Age in 70 Healthy Children
Authors: Lestradet H , Deschamps I , Giron B
Published: September 2013

In 70 healthy children aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acids were measured during a three-hour glucose tolerance test. The results are presented for the whole group as well as for three age groups: three months-five years, six-10 years, and 11–15 years.

It is demonstrated that (1) glucose levels are significantly lower in young children (younger than five years); (2) there are no significant age-related changes in free fatty acid concentration; (3) insulin levels are increasing constantly and significantly with age, the most strikingly at the age of onset of puberty; the absence of notable changes in glucose tolerance results in a rise of the I/G ratio as well.

The causes for the increase of insulin secretion with age, whether of peripheral or pancreatic order, are still speculative.
Interaction of Alloxan and Anomers of D-Glucose on Glucose-induced Insulin Secretion and Biosynthesis in Vitro
Authors: Niki Atsushi , Niki Hatsumi , Miwa Ichitomo , Lin Boniface J
Published: September 2013

The direct effects of alloxan on glucose-induced insulin secretion and biosynthesis and the interaction of alloxan and D-glucose anomers were studied in vitro by use of isolated islets from rat pancreas. Islets were pretreated by incubation for five minutes in media containing alloxan (0.2 mg./ml.) alone or alloxan with either the α or β anomer of D-glucose (3 mg./ml.). After washing, batches of five islets were incubated in the medium supplemented with glucose (1.8 mg./ml.) for 60 minutes to observe insulin secretion and for 90 minutes to observe insulin biosynthesis. Prior exposure to alloxan alone produced marked inhibition of subsequent glucose-induced insulin secretion and biosynthesis. A significantly greater protection against these inhibitory effects of alloxan was observed by using the α anomer of D-glucose than the β anomer. The anomeric preference of D-glucose for protecting islet cells from the inhibitory effect of alloxan on glucose-induced insulin secretion and biosynthesis was similar to that for triggering insulin secretion. Possible mechanisms of the inhibitory effect of alloxan and the protective effect of D-glucose anomers in connection with those of other sugars are discussed. It is suggested that a glucoreceptor, stereospecific to the α anomer of D-glucose, may exist for both insulin secretion and biosynthesis.
Inhibition of Lymphocyte Blastogenesis by Factor(s) in Alloxan-diabetic Rat Plasma
Authors: Pallavicini Maria G , Nichols William K
Published: September 2013

Supplementation of rat lymphocyte cultures with plasma from alloxan-diabetic rats produced a dose-dependent suppression of mitogen-induced blastogenic responses. Viability measurements indicated that this inhibition was not due to a direct cytotoxic effect of alloxan-diabetic plasma on rat mononuclear leukocytes in vitro. This inhibition was not explained by hyperglycemia alone and was observed when blastogenesis was induced in vitro by phytohemagglutinin (PHA), concanavalin A (con A), or allogeneic cells. Peripheral blood lymphocytes from alloxan-diabetic rats appeared to be more sensitive than normal cells to the inhibitory effect of diabetic plasma.

Heating at 56° for 60 minutes produced only a partial loss of the inhibition by diabetic plasma. Alloxan-diabetic rat plasma promoted an increased accumulation of adenosine 3′,5′-monophosphate (cyclic AMP) in mononuclear leukocytes. Insulin (1 and 100 μU./ml.) in vitro enhanced PHA-induced blastogenesis but failed to reverse the inhibition caused by diabetic plasma. Ultrafiltration through a cellulose dialysis membrane with an exclusion size of 12,000 molecular weight did not remove the inhibitory factor(s).

These results indicate that a depressed cellular immune response is produced during an insulin-deficient diabetic state. The suppressed in-vitro blastogenic response of lymphocytes from alloxan-diabetic rats appears to involve some circulating inhibitory factor(s) in diabetic plasma. This inhibition may be explained, in part, by the ability of diabetic plasma to elevate cyclic AMP in mononuclear leukocytes.
Standardization of a Digestion-filtration Method for Isolation of Pancreatic Islets
Authors: Shibata Atsumi , Ludvigsen Carl W , Naber Stephen P , McDaniel Michael L , Lacy Paul E
Published: September 2013

Standardization of a technic for isolating large numbers of pancreatic islets is described. This procedure employed collagenase digestion of rat pancreatic tissue in a cylindrical wire screen in order to separate isolated islets from undigested pancreas. From this basic protocol the following conditions were established: (1) the duration of the initial digestion period was found to be optimal at six minutes; (2) three subsequent digestions of one minute each effected maximum islet yield; (3) the optimal initial collagenase concentration was found to be 1,000 U. (Worthington)/ml.; and (4) proper reductions of collagenase concentrations during the three subsequent digestions were found to be 50 per cent of each preceding incubation period. This method, combined with Ficoll gradient separation, yielded a mean of 800 islets per two rat pancreases. The isolated islets appeared morphologically intact, contained 0.36 ± 0.05 μg. protein/islet, and demonstrated a normal biphasic release of insulin in response to stimulative levels of D-glucose. The present method provides a means for obtaining a large mass of viable islet cell tissue in a short time.
Immunopathology of Renal Extracellular Membranes in Diabetes Mellitus: Specificity of Tubular Basement-membrane Immunofluorescence
Authors: Miller Kenneth , Michael Alfred F
Published: September 2013

This study documents the presence of marked immunofluorescence for IgG and albumin in renal extracellular membranes, especially tubular basement membranes (TBM), of patients with severe diabetic nephropathy. A comprehensive immunofluorescent analysis was carried out on kidney tissue from 83 patients—Group I: 24 living normal renal allograft donors and two infants less than one week of age. Group II: 24 patients with severe nephropathy who had juvenile onset of diabetes 16 to 30 years previously and who ranged in age from 20 to 47 years. Group III: 33 patients with severe kidney disease of varied etiologies with an age range of five to 63 years. The sections were assayed for a variety of proteins (immunoglobulins, complement components, and tissue antigens). Kidney sections of all patients with severe diabetic nephropathy were readily distinguished from kidneys of other patients and normals by the intense linear staining of the extracellular membranes, especially the tubular basement membrane, for IgG and albumin. Dual-labeled studies using FITC anti-basement-membrane (BM) and tetramethyl rhodamine (TMR) antialbumin demonstrated localization of the albumin predominantly to the outer but also the inner TBM while the BM antisera reacted more intensely with the inner membrane. There is no evidence that an immunologic process is responsible for these Findings.

These immunofluorescent findings are specific for severe diabetic nephropathy and may reflect structural changes in the renal extracellular membranes that permit entrapment of serum proteins, possibly due to changes in permeability.
Nodular Intercapillary Glomerulosclerosis in Diabetes Secondary to Chronic Calcific Pancreatitis
Authors: Wellmann Klaus F , Volk Bruno W
Published: September 2013

Nodular (specific) intercapillary glomerulosclerosis (Kimmelstiel-Wilson) was found at autopsy in a 47-year-old man who had been diabetic for 20 years. The family history for this disease had been negative. Both the clinical course and the autopsy findings strongly suggest that this patient's diabetes was secondary to chronic fibrocalcific pancreatitis. This is only the fourth recorded case of histologically documented nodular glomerulosclerosis occurring in a patient with pancreatogenic diabetes.
Is Cigarette Smoking More Frequent Among Insulin-treated Diabetics?
Authors: Czyżyk Artur , Królewski Andrzej S
Published: September 2013

During epidemiologic investigations of vascular complications of diabetes in Warsaw the habit of cigarette smoking was analyzed in the subjects studied (4,530 diabetics). It was found that in the group of diabetics the number of ex-smokers was much greater (p < 0.01) and that of present smokers lower (p < 0.01) than in a representative sample of the Warsaw population. Furthermore, it was observed that in the subgroup of insulin-treated diabetics the number of smokers was highest and the number of ex-smokers and nonsmokers was lowest in relation to other treatment subgroups.
Postheparin Plasma Lipoprotein Lipase and Hepatic Lipase in Diabetes Mellitus: Relationship to Plasma Triglyceride Metabolism
Authors: Nikkilä Esko A , Huttunen Jussi K , Ehnholm Christian
Published: September 2013

The activity of two triglyceride Upases was determined by an immunochemical method in the postheparin plasma of 60 diabetic patients and of 47 age- and sex-matched nondiabetic control subjects. The results were related to the type of diabetes, to plasma triglyceride and insulin concentrations, to removal of exogenous fat from the blood, and to turnover of VLDL-triglycerides. The mean postheparin plasma lipoprotein lipase (LPL) activity was decreased by 44 per cent (p < 0.001) in patients with untreated ketotic diabetes and by 20 per cent (P < 0.01) in patients with untreated mild to moderate nonketotic early-onset diabetes. Insulin treatment of ketotic diabetes resulted in a rapid increase in the activity of LPL and decrease in serum triglyceride level, whereas sulfonylurea treatment of non-insulin-requiring diabetics did not significantly influence the enzyme activity. In insulin-treated chronic diabetics the average postheparin plasma LPL activity was not different from that of nondiabetic controls, but some of these patients had high LPL values. In normolipidemic maturity-onset-type diabetics the LPL activity was within normal range, but in those having hypertriglyceridemia the average LPL value was decreased by an average of 26 per cent (P < 0.01).

The LPL activity showed a significant negative correlation with the logarithm of serum triglyceride concentration (r = −0.62) and a positive correlation with fractional removal of Intralipid (r = +0.64) and fractional turnover of VLDL triglyceride (r = +0.40). The activity of LPL was correlated to basal plasma insulin concentration in insulin-deficient diabetics (r = +0.34) but not in patients with maturity-onset-type diabetes. The hepatic lipase (HL) activity of postheparin plasma was similar in diabetics and controls, with the exception of hypertriglyceridemic maturity-onset diabetics, who had higher mean HL activity than the corresponding control group (p > 0.01). The activity of HL was not related to triglyceride removal but showed a significant correlation to VLDL-triglyceride production rate.

On the basis of these results it seems that a deficiency of LPL accounts for a great deal of the elevation of serum triglyceride in insulin-deficient human diabetes but has a smaller role in the pathogenesis of the hypertriglyceridemia that is associated with maturity-onset diabetes. The latter abnormality is caused mainly by an increased secretion of triglycerides into the blood even though a decreased LPL may contribute to development of hyperlipemia in cases with gross elevation of serum triglycerides.
Incidence and Significance of Islet-cell Autoantibodies in Different Types of Diabetes Mellitus
Authors: Prete Gian Franco Del , Betterle Corrado , Padovan Domenico , Erle Giuseppe , Toffolo Antonella , Bersahi Giorgio
Published: September 2013

Islet-cell (ICA) and organ-specific autoantibodies (OSA) were determined by the indirect immunofluorescence technique in 920 diabetics, 1,159 nondiabetic patients, and 100 young and 100 adult healthy controls with normal glucose tolerance. In control subjects ICA were not detected, and only 20 miscellaneous patients with normal glucose tolerance showed ICA (1.7 per cent). ICA were present in 45.4 per cent of patients with juvenile insulin-dependent diabetes (IDD) during the first six months of disease and in 29.1 per cent of patients between 6 and 12 months of disease onset; ICA presence decreased to 19.2 per cent and 20.6 per cent after one and five years of duration of diabetes.

In patients with maturity-onset IDD, ICA incidence was 19.4 per cent in the first year, 20 per cent between one and five years, and 12.2 per cent after five years of disease. In this group, 64 per cent of ICA-positive patients showed clinical and/or serologie evidence of thyroid, gastric, or adrenal autoimmune disorders.

In sera from young patients with non-insulin-dependent diabetes (J-NIDD), ICA were not detected. In adult patients with the same type of diabetes (M-NIDD) ICA incidence was 9.8, 7, and 8.9 per cent and was not related to the duration of diabetes. Patients with chemical diabetes were divided into two groups (younger and older than 35 years), and ICA incidence was 18.9 and 12.9 per cent, respectively. In two nondiabetic patients, glucagon cell autoantibodies were detected. ICA titers were variable in juvenile IDD of recent onset. Persistent ICA titers, frequently associated with OSA, were observed in the other types of diabetes, with the exception of J-NIDD. ICA may be considered markers of severe beta-cell alteration, with consequent reduction of insulin secretion, even though insulin dependency is sometimes delayed in a few patients.
Brittle Diabetes in Pregnancy
Authors: Lev-Ran Arye , Goldman Jack A
Published: September 2013

In eight brittle diabetics the insulin requirement increased during successful pregnancies from 35 to 64 U ./day (in 29 stable severe diabetics from 53 to 78 U./day). The within-day glycemie excursions were calculated as the mean of the three differences between four time points: fasting, one hour after breakfast, two hours after breakfast, and two hours after lunch. This parameter was constant throughout the pregnancy in nondiabetics (34-46 mg./100 ml.) and stable severe diabetics (55-72 mg./100 ml.). In brittle diabetics itdropped from 147 mg./100 ml. before the pregnancy and 153 mg/100 ml. at eight weeks to 85 mg./100 ml. at 36 weeks. The between-day variability was calculated as the mean glycemie difference between two successive days at the four points of time noted above. It was very low in nondiabetics (12-16 mg/lOO ml.) and much higher in stable diabetics (49-53 mg./100 ml.). In brittle diabetics it decreased from 127 mg./100 ml. before pregnancy and 120 mg./100 ml. at eight weeks to 46-55 mg./100 ml. at 24-36 weeks. This shows that brittleness substantially decreased in the second half of pregnancy.
Plasma Cyclic Nucleotide Levels in Juvenile-onset Diabetes
Authors: Goldberg Melvin L , Bohannon Nancy V , Brooks Robert M , Tsalikian Eva , Lorenzi Mara , Forsham Peter H
Published: September 2013

In patients with juvenile-onset diabetes, plasma concentrations of 3',5'-adenosine cyclic monophosphate (cAMP) were significantly lower than those of normal subjects [16 ± 4 and 24 ± 7 pmol per milliliter (p <0.025), respectively] as determined in this laboratory; whereas there were essentially no differences in plasma levels of 3',5'-guanosine cyclic monophosphate (cGMP). Because CAMP inhibits cell growth and cGMP stimulates it, these findings may represent an important factor in the atherosclerotic and obliterati ve angiopathies of diabetic individuals. We observed that cyclic nucleotide values were the same whether or not the subjects were receiving insulin. Those given insulin plus enough glucose to maintain hyperglycemia revealed modest elevations in cyclic nucleotide levels. Thus, the ratio of cAMP to cGMP, abnormally low in juvenile-onset diabetes, is relatively independent of short-term variations in plasma levels of either glucose or insulin.
Pregnancy in Diabetes Complicated by Vascular Disease
Authors: Hare John W , White Priscilla
Published: September 2013

Over 50 years of experience with pregnancy in diabetic women is reviewed. In particular, the maternal and fetal survival in mothers with either microvascular or macrovascular disease is considered. This includes White classes E, F, R, RF, H, and T. In this group of patients with vascular disease, maternal survival during pregnancy is virtually 100 per cent with the exception of class H (ischemie heart disease). Fetal survival has steadily improved throughout the time period examined, but is still considerably below that of pregnancies occurring in women without vascular disease. Long-term maternal survival is adversely affected by the first decade after delivery.
In-vivo Measurement of Glucose and Alanine Metabolism with Stable Isotopic Tracers
Authors: Bier D M , Arnold K J , Sherman W R , Holland W H , Holmes W F , Kipnis D M
Published: September 2013

This report describes sensitive, precise microtechniques that allow quantification of glucose and alanine metabolism in vivo using stable isotope tracers. By combined gas chromatography-mass spectrometry and selected ion monitoring—deuterium and carbon-13 enrichment in blood glucose and alanine were measured with an error of less than 2 per cent. Estimation of glucose and alanine flux in dogs by stable isotope tracer techniques was compared with simultaneous measurements made in the same animal with conventional radiotracer dilution methods. Application of the described stable isotope methods to determination of glucose and alanine turnover as well as alanine-2,3-l3C incorporation into glucose In adult men confirmed the safety and validity of these techniques for human investigation.
Lipid Metabolism in Pregnancy: V. Interactions of Diabetes, Body Weight, Age, and High Carbohydrate Diet
Authors: Warth Maria R , Knopp Robert H
Published: September 2013

Plasma triglycerides increase two-to-three-fold in normal pregnancy. If mechanistically similar to the atherosclerosis-associated hypertriglyceridemias, hypertrigiyceridemia in pregnancy should be exaggerated by diabetes, obesity, and high carbohydrate feeding. A failure to exaggerate would point to a different physiologic mechanism. To study this matter, we measured fasting plasma triglyceride and cholesterol in 38 normal, 22 gestational-diabetic, and 27 overtly diabetic women in the third trimester, measuring the concomitant effects of age and body weight and, in four subjects, high carbohydrate feeding.

Compared with controls, fasting plasma triglyceride and cholesterol were unchanged in gestational diabetics and in 10 of the 27 overtly diabetic pregnant women treated with insulin and diet. However, 17 of 27 diabetic women treated with an estrogen-progestin supplement during gestation had a 36 per cent higher triglyceride and a 15 per cent higher cholesterol than control. Body weight, age, duration of diabetes, or length of gestation could not account for the observations. In non-hormone-treated subjects, regression analysis showed a positive correlation of triglycerides with age but not with body weight. High carbohydrate feeding in pregnancy produced a triglyceride increase (mean±S.D.) of 9±19 per cent in whole plasma and 17±13 per cent in very-low-density Upoprotein. Respective postpartum increases were 41 and 68 per cent, similar to the responses reported in nonpregnant individuals.

Conclusion: Lack of a major effect of diabetes, body weight, and high carbohydrate feeding on blood lipids in gestation distinguishes pregnancy from the atherosclerosis-associated hypertriglyceridemias and points to a different physiologic control mechanism.
Comparison of Highly Inbred Diabetic and Nondiabetic Lines in the Upjohn Colony of Chinese Hamsters
Authors: Chang Albert Y , Noble Robert E , Wyse Beatrice M
Published: September 2013

Eighteen Chinese hamsters, each from two highly inbred lines XA (glucosurie) and M (aglucosuric), were studied with regard to their insulin and glucagon reserves, liver and epididymal fat pad enzymes, and kidney glycosidases. Reciprocal perturbation in pancreatic insulin and pancreatic and stomach glucagon was found in the diabetic XA line, and the degree of disturbance increased with the severity of hyperglycémie. Depression in glucokinase and elevation in phosphenolpyruvate carboxykinase were observed in the livers of all XA animals, whereas decreases in hepatic pyruvate klnase and 6-phosphogluconate dehydrogenase occurred only in XA animals with prolonged diabetes. The levels of these and other enzymes were found to be normal in the epididymal fat pad of the XA animals. Difference in lactate dehydrogenase isozyme distribution was detected in both liver and fat pad between XA and M lines and was attributed to genetic variance. The XA animals showed an elevated level of plasma N-acetyl-β-glucosaminidase but had a similar level of this enzyme in the kidney as the M line, α- and β-galactosidase are significantly depressed in the kidney of the XA animals, whereas αand β-glucosidase are not. Thus, reciprocal disturbances in tissue insulin and glucagon reserves are present in spontaneous diabetes in the Chinese hamsters, and the deviant levels of enzymes in such tissues as liver and kidney may contribute to the manifestation of hyperglycemie and diabetic complications.
Deranged Insulin-secretory Dynamics in Offspring of Two Diabetic Parents After Double Stimulation with Intravenous Glucose
Authors: Koncz L , Soeldner J S , Otto H , Smith T M , Gleason R E
Published: September 2013

Nine offspring of two diabetic parents and 18 normals were studied with two intravenous glucose loads (0.5 gm./kg. body weight), 60 minutes apart. By thus stressing the beta cell, subtle defects could be identified in the prediabetics: (1) An inverse relationship between insulin peak response and insulin concentration 60 minutes postglucose was seen, a phenomenon exactly the opposite to that seen in normals. (2) Insulin peak response was delayed slightly after the first pulse and significantly after the second. (3) A less effective handling of the glucose load when compared with normals was brought out by the second stimulation. (4) There was a significant reduction in the insulin response per unit change in glucose after the first glucose pulse that was accentuated after the second pulse. This double-stimulation technique amplifies previously detected slight but significant defects in insulin secretion that might help to identify a diabetes-prone population.
Pancreatic Islet-cell Antibodies in Diabetes Mellitus Correlated with the Duration and Type of Diabetes, Coexistent Autoimmune Disease, and HLA Type
Authors: Irvine W J , McCallum C J , Gray R S , Campbell C J , Duncan L J P , Farquhar J W , Vaughan H , Morris P J
Published: September 2013

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral bypoglycemk agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects.

In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent on the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10–20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account.

Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative.

Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.
Does Insulin Need a Second Messenger?
Authors: Goldfine Ira D
Published: September 2013

It is well established that specific binding sites for insulin are present on the plasma membranes of target tissues. In order to explain how insulin regulates a wide variety of biologic functions both on the surface of the cell as well as in its interior, it has been postulated that insulin generates a second messenger at the cell surface. To date, however, no second messenger for insulin has been identified that can carry out all of insulin's known actions. Recent studies have demonstrated that, in addition to the plasma membrane, other subcellular organelles, such as the nucleus, have specific binding sites for insulin. There is also evidence indicating that large serum proteins such as albumin, large protein hormones such as prolactin, and small protein hormones such as insulin can enter intact cells. It is hypothesized, therefore, that insulin has at least two mechanisms of action on target tissues. One mechanism entails the direct binding of insulin to the plasma membrane, which in turn leads to its well-known effects on membrane transport. The other mechanism requires the entry of insulin itself into the interior of the cell and its subsequent direct binding to subcellular organelles. This latter process then serves to mediate many of the known intracellular functions of insulin.
Tolbutamide-induced Hemolytic Anemia
Authors: Malacarne Paolo , Castaldi Giuseppe , Bertusi Maurizio , Zavagli Giorgio
Published: September 2013

A 67-year-old female diabetic is presented who developed a Coombs'-positive hemolytic anemia after a year of treatment with tolbutamide. An IgG antibody was identified in the patient's serum that caused the agglutination of both the patient's red blood cells and tolbutamide-coated erythrocytes in the absence of complement. Such a reaction did not occur with the patient's erythrocytes when not exposed to tolbutamide. Agglutination of the patient's serum also occurred with erythrocytes treated with other sulfonylureas (chlorpropamide, glibendamide, carbutamide) but not with phenacetin.
Dietary Intake and Hyperlipidemia in Controlled Diabetic Outpatients
Authors: Maruhama Yoshisuke , Abe Ryuzo , Okuguchi Fuminobu , Ohneda Akira
Published: September 2013

Statistical analyses were performed in order to determine the effects of the control of the diabetes as well as the food intake on serum lipid levels of 73 diabetic outpatients. They had had elevated fasting blood glucose levels, mostly complicated by various grades of hyperlipidemia, before the initiation of treatment. Hyperlipidemia was found to be ameliorated in nearly half of those patients after the start of diabetic treatment. However, the elevation of serum triglyceride persisted in 30 per cent of controlled diabetics, and no differences were found in occurrence of hypertriglyceridemia between diet-treatment group, sulfonylurea group, biguanide group, combined group and insulin group. Estimation of diet intake revealed that the controlled hypertriglyceridemic patients consumed slightly (but significantly) greater amounts of sucrose, alcohol, and total calories than the controlled normotriglyceridemic patients. In addition to such inadequate diet consumptions, the tendency to be overweight and the subtle increment of fasting blood glucose levels were also shown to have contributed to hypertriglyceridemia. It is thus concluded that the lipid disorder in controlled diabetic outpatients is the result of multifactorial influences and that well-conducted diet therapy and stricter regulation of blood glucose are essential in the management of posttreatment hyperlipidemia.
Species Variation in Pancreatic Islet Monoamine Uptake and Action
Authors: Mahony Cheryl , Feldman Jerome M
Published: September 2013

There are conflicting data in the literature regarding the role of monoamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotonin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemie mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monoamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C 5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation in the uptake of these monoamines and their precursors.
Investigation of Insulin Sensitivity in Treated Subjects with Ketosis-prone Diabetes Mellitus
Authors: Ginsberg LCDR Henry N
Published: September 2013

Two similar intravenous infusion techniques have been utilized to investigate insulin sensitivity in young subjects with recent-onset ketosis-prone diabetes mellitus. All subjects presented initially with mild to moderately severe ketoacidosis and had been treated with daily insulin therapy for two to eight weeks at the time of study.

Six diabetics and 10 normal subjects (group A) received intravenous infusions of glucose (6 mg./kg./min.), insulin (80 mU./min.), epinephrine (6 μg./min.), and propranolol (0.08 mg./min.) for ISO minutes. Steady-state plasma glucose (SSPG) and insulin levels (SSPI) were reached by 90 minutes and maintained through the end of the study. As all subjects achieve similar SSPI while simultaneously receiving similar glucose loads, the SSPG can be used to measure individual insulin sensitivity. Under these conditions the diabetics in group A had a mean SSPG (± S. E.) of 99 ± 26 mg./lOO ml., which was not different from the level of 98 ± 14 mg./100 ml. for their control subjects. Six diabetics and six normal subjects (group B) received infusions of only glucose (6 mg./kg./min.) and insulin (80 mU./min.). Similar SSPI levels were attained in both the diabetic and control subjects, and their mean SSPG (± S.E.) levels were not significantly different (83 ± 13 vs. 61 ± 6mg./100 ml.).

One diabetic in group A and two diabetics in group B had SSPG levels above the highest values measured in their control groups. However, all three had markedly elevated fasting plasma glucose levels on the day of study. In contrast, nine well-controlled diabetics had normal insulin sensitivity. These results suggest that well-controlled subjects with ketosis-prone diabetes mellitus have normal sensitivity to insulin.
2,3-Diphosphoglycerate, Nucleotide Phosphate, and Organic and Inorganic Phosphate Levels During the Early Phases of Diabetic Ketoacidosis
Authors: Kanter Y , Gerson J R , Bessman A N
Published: September 2013

The relation between serum and red blood cell (RBC) inorganic phosphate levels, RBC 2,3-diphosphoglycerate (2,3-DPG) levels, RBC nucleotide phosphate (Pn), and RBC total phosphate (Pt) levels were studied during the early phases of treatment and recovery from diabetic ketoacidosis (DKA).

A steady drop in serum inorganic phosphate was found during the first 24 hours of insulin treatment and was most profound at 24 hours. No statistically significant changes (P>0.05) were found in red cell inorganic phosphate or nucleotide phosphate levels during the 24-hour study period. The levels of total red cell phosphate were lower in this group of patients than in nonacidotic diabetic subjects and decreased slightly after 24 hours of treatment. The red cell 2,3-DPG levels were low at the initiation of therapy and remained low during the 24-hour study period. Glucose, bicarbonate, lactate, and ketone levels fell in linear patterns with treatment.

In view of the current evidence for the effects of low 2,3-DPG on oxygen delivery and the relation of low serum phosphate levels to RBC glycolysis and 2,3-DPG formation, this study reëmphasizes the need for phosphate replacement during the early phases of treatment of DKA.
The Prognostic Importance of Plasma Glucose Levels and of the Use of Oral Hypoglycemic Drugs After Myocardial Infarction in Men
Authors:   Coronary Drug Project Research Group
Published: September 2013

The relationship of plasma glucose levels to risk of death over a five-year follow-up period was studied in 2,770 male survivors of myocardial infarction in the placebo group of the Coronary Drug Project (CDP). In uni variate analyses, a positive association was observed between mortality rates and both fasting and one-hour glucose levels. After adjustment for 38 other baseline characteristics, the strengths of these relationships were substantially diminished; however, an increased mortality persisted in patients with fasting glucose levels 5≥140 mg./dl. after adjustment for other risk variables. There exists some evidence of an increased mortality risk in users of oral hypoglycemic (OH) agents over that of nohusers at baseline in men with elevated baseline glucose levels. However, the results must be interpreted with great caution both because they are of only borderline statistical significance and also because various factors not recorded in the CDP might have influenced the results.
Diabetes and Neutrophil Chemotaxis
Authors: Fikrig Senih M , Reddy Churku M , Orti Eduardo , Herod Llewellyn , Suntharalingam Kamala
Published: September 2013

The chemotaxis of PMN cells from adult and juvenile diabetics and proper control subjects was found to be comparable. Similarly, chemotactic activity generated from diabetic sera was not different from the activity generated from the normal sera.
Mechanism of Hypoglycemia Observed in a Patient with Insulin Autoimmune Syndrome
Authors: Ichihara Kikuo , Shima Kenji , Saito Yoshikazu , Nonaka Kyohei , Tarui Seiichiro , Nishikawa Mitsuo
Published: September 2013

A 21-year-old female patient complaining of frequent hypoglycemie attacks in the presence of a large amount of circulating insulin-binding antibodies without prvious known immunization is described.

In order to clarify the possible mechanism of the hypoglycemie attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C-peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies was also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 ml. at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 μU./ml. was registered at 180 minutes, while the peak value of free IRI of 208 /μU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 × 109M−1).

Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemie attack in the patient.

The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.
Correlation of Serum Triglyceride Levels and Hemoglobin AIc Concentrations in Diabetes Mellitus
Authors: Peterson Charles M , Koenig Ronald J , Jones Robert L , Saudek Christopher D , Cerami Anthony
Published: September 2013

Studies in 10 nonketotic diabetic subjects (five juvenile- and five adult-onset) before and after control of carbohydrate metabolism showed a high degree of correlation between hemoglobin AIc (Hb AIc) concentrations and serum triglyceride levels. Serum triglyceride levels were found to correlate more dosely with Hb AIc (r = 0.91, p < 0.001) than did serum cholesterol (r = 0.47, p > 0.05), thus indicating a more direct relationship to carbohydrate metabolism.
Metabolie Approaches to Studies on Diabetic Microangiopathy
Authors: Waitzman M B , Colley A M , Nardelli-Olkowska K
Published: September 2013

The chief purposes of this report are (a) to focus attention on various metabolic and pathophysiologic parameters relating prostaglandins (PGs) and thromboxanes to the slow but inexorable progression of vascular and blood cell dysfunction in diabetes mellitus and (b) to suggest areas of investigation that may be of fundamental importance for expanded areas of diabetes research. The prime thrust of these investigations would be to correlate these metabolic and pathophysiologic parameters with the vasculopathy of diabetes mellitus.
Intravenous Insulin Causing Loss of Intravascular Water and Albumin and Increased Adrenergic Nervous Activity in Diabetics
Authors: Gundersen H J G , Christensen N J
Published: September 2013

Blood pressure, heart rate, plasma norepinephrine, forearm blood flow, plasma volume, plasma albumin, blood glucose, and plasma epinephrine were measured in six diabetic patients without neuropathy in the supine position and during feet-down tilting for seven minutes. The experiments were repeated after intravenous (i.v.) injection of 6 to 8 U. of insulin.

The mean blood glucose concentration averaged 205 ± 14 (S. E. M.) mg./100 ml. in the control experiment and had decreased by 97 ± 17 mg./100 ml. 45 minutes after the injection of insulin. None of the patients had hypoglycemia, and plasma epinephrine did not increase.

There was no change in arterial blood pressure after insulin was given either in the supine position or after tilting. The heart rate averaged 64 ± 5 beats per minute in the control experiment and had increased by 7 ± 2 beats per minute 40 minutes after the injection of insulin (2p = 0.035). The rise in heart rate In response to tilting was statistically significantly greater after administration of insulin (2p = 0.0064).

Plasma norepinephrine averaged 0.17 ± 0.03 ng./ml. in the control experiment and had increased by 70 ± 24 per cent 45 minutes after the i.v. injection of insulin (2p = 0.045). The rise in plasma norepinephrine in response to tilting was statistically significantly greater after the injection of insulin (2p = 0.017).

Forearm blood flow decreased from 2.13 ± 0.29 ml./l00 ml. per minute in the control experiment to 1.63 ± 0.32 ml./100 ml. per minute 40 minutes after the injection of insulin (2p = 0.011). Plasma volume averaged 3,061 ± 67 ml. before injection of insulin and had decreased by 265 ± 59 ml. 45 minutes after insulin was given (2p = 0.011). The intravascular mass of albumin averaged 118 ± 3 gm. and 109 ± 3 gm. before and 45 minutes after the administration of insulin, respectively (2p = 0.017).

There was a dose correlation between the relative increase in plasma norepinephrine in the supine position and the relative decrease in plasma volume after the injection of insulin (r = −0.95, 2p = 0.013).

It is concluded that i.v. injection of insulin results in an increased adrenergic nervous activity that is due to a decrease in plasma volume. The effect of insulin is accompanied by a significant reduction in the intravascular pool of albumin.

These observations may explain the fact that patients with abnormal cardiovascular reflexes are unable to maintain arterial blood pressure, especially in the upright position, after the i. v. injection of insulin.

The observed decrease in plasma volume after the administration of insulin was much larger than could be expected from the decrease in blood glucose concentration and the ensuing decrease in plasma osmolality.

It is suggested that insulin either directly or secondarily to its metabolic effects may alter the function or the volume of the endothelial cells and thereby increase the transfer of fluid and albumin out of the vascular system.
A Three-year Controlled Follow-up Study of Persons Identified in a Mass Screening Program for Diabetes
Authors: Houser Harold B , Mackay Wilma , Verma Narendra , Genuth Saul
Published: September 2013

Each of 529 persons identified as positive in a diabetes mass screening industrial program was matched with a negative screenee of the same sex, race, age, and place of employment. A confirming glucose tolerance test classified the positive screenees into three groups: confirmed (204), not confirmed (141), and not tested (184). The confirmed group was slightly older than the other two groups. A three-year follow-up by means of a mail questionnaire showed that death occurred more frequently in confirmed positives (7 per cent); the self-perceived, current health state was poorer for the confirmed positives than for their controls, with no differences between the other positive and control groups; and significant weight loss occurred in confirmed and not tested positives. A positive screening test resulted in increased early contact with physicians, but only confirmed positives had evidence of continuing increased contact. Oral antidiabetic medications were currently prescribed for 28, 17, and 1 per cent, respectively, for the confirmed, the not tested, and the not confirmed positives. With no clear evidence of modification of the subjects' behavior toward continued medical care and, considering the potential harm of improper or early exhibition of oral drugs or the incorrect labeling of persons as diabetic, the possible benefits of early physician intervention and weight loss do not appear to offset the potential nonbenefit of mass screening. These conclusions have resulted in modification of the Cleveland program to one of discriminate screening rather than indiscriminate mass screening.
Serum Phenformin Concentrations in Patients with Phenformin-associated Lactic Acidosis
Authors: Conlay L A , Karam J H , Matin S B , Loewenstein J E
Published: September 2013

Phenformin concentrations were measured in serum from seven patients with phenformin-associated lactic acidosis, and initial values ranging from 20 to 625 ng./ml. were obtained. Five of the seven patients had serum concentrations within the usual therapeutic range of up to 241 ng./ml. Serum phenformin concentrations were measured serially, and apparent half-lives of 5, 25, and 30 hours were obtained in three patients with serum creati nine concentrations of 1.7, 7.6, and 6.0 mg./dl., respectively. Although the half-life of phenformin was prolonged in azotemic patients, no correlation between serum creatinine concentration and serum phenformin could be demonstrated; furthermore, the severity of lactic acidosis as measured by arterial pH and lactate concentration did not correlate with the serum creatinine concentration.
Physiologic Role of Somatostatin Insulin Release from Rat Islets Treated by Somatostatin Antiserum
Authors: Taniguchi Hiroshi , Utsumi Masafumi , Hasegawa Masami , Kobayashi Tetsuo , Watanabe Youzo , Murakami Keiji , Seki Michio , Tsutou Akimitsu , Makimura Hiroyuki , Sakoda Masahiro , Baba Shigeaki
Published: September 2013

In order to clarify the physiologic role of somatostatin in insulin release, rat pancreatic islets treated by somatostatin antiserum were incubated in media containing various concentrations of glucose. Insulin release from antiserum-treated islets was significantly elevated above that from nontreated ones at 3.3 and 8.3 mM glucose, while the former was not different from the latter at 16.7 mM glucose. It is suggested that somatostatin plays an important role in the regulation of insulin release in the physiologic range of glucose concentration.
Enzyme Studies in the Articular Cartilage of Diabetic Rats and of Rats Bearing Transplanted Pancreatic Islets
Authors: Silberberg R , Hirshberg G E , Lesker P
Published: September 2013

The articular cartilage of normal rats, of rats made diabetic with streptozotocin, and of rats made diabetic with streptozotocin and subsequently transplanted with isologous pancreatic islets was examined for the activities of enzymes engaged in the synthesis and degradation of glycosaminoglycans (mucopolysaccharides). The activities assayed were those of the degrading enzymes B-glucuronidase, B-acetyglucosaminidase, B-acetylgalactos-aminidase, B-galactosidase, and those active in synthesis: uridine-diphosphate dehydrogenase, ghicose-6-phosphate dehyrogenase, and phosphofructokinase. In the diabetic animals all enzyme activities were increased, those of the degrading enzymes more than those of the others. Implantation of pancreatic islets reversed the changes produced by diabetes, enzyme activities returning to near-normal levels.
Identification of Four Cell Types in the Human Endocrine Pancreas By Immunoelectron Microscopy
Authors: Pelletier Georges
Published: September 2013

In order to correlate the different cell types of the human endocrine pancreas to a specific secretion product, an immunoelectron microscopic localization of the hormones whose production had been attributed to pancreatic islets was conducted. Glucagon and insulin were respectively localized in the typical A- and B-cells, whereas no subclasses of A-cells could be identified. With antibodies that reacted with the gastrin cells in the human gastric mucosa, it was not possible to detect gastrin in any of the islet cell types. In confirmation of recent results obtained by light microscopy, somatostatin was found in all the typical D-cells containing large, weakly electron-dense secretory granules. The human pancreatic polypeptide (HPP), a newly postulated hormone, was clearly associated with a fourth cell type, which is characterized by the presence of small secretory granules (100–150 nm.). These results suggest that each of the four cell types that are easily identifiable by ultrastructural observations is responsible for the production of a specific secretory product.