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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycemia induced in animals by beta cell toxins or by pancreatectomy can be reversed by pancreatic islet transplantation. Abnormal carbohydrate metabolism in juvenile onset human diabetics has also been corrected, albeit temporarily because of graft rejection, by pancreatic transplantation. It does not necessarily follow that naturally occurring diabetes in animals or adult onset diabetes in man would respond to similar treatment. Islet transplantation was studied in mice with chemically induced or genetically determined diabetes. Streptozotocin-induced diabetic mice were permanently cured by syngeneic islets and, when immunosuppressed, were rendered normoglycemic for six weeks after receiving xenogeneic rat islets. In contrast, histocompatible islets from normoglycemic coisogenic donors were ineffective in hyperglycemic db/db recipients as were xenogeneic rat islets in immunosuppressed db/db hosts. However, when islets were isolated from db/db donors and transplated to genetically normal coisogenic mice, which had been rendered hyperglycemic with streptozotocin, they became normoglycemic. Apparently the metabolic defect in the db/db mice, which is similar in some ways to human maturity onset diabetes, does not reside in their islets as these cells can function normally if transplanted to genetically nondiabetic hosts. In two other types of genetic diabetes (ob/ob and NZO) islet transplantation was more effective. Pancreatic transplantation is unlikely to be the proper treatment for all types of diabetes even if technical and immunological problems are overcome.
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PMID:Islet transplantation in genetically determined diabetes. 14 16

Nonketotic hyperosmolar diabetic coma is a rare manifestation of juvenile diabetes, in contrast to adult onset diabetes. To date only 20 cases have been published, the majority of them infants and toddlers. This type of diabetic coma is seen with unusual frequency in children with Down's syndrome and psychomotor retardation. The clinical picture is characterised by severe dehydration, hyperglycemia with often extremely high blood sugar levels, hyperosmolarity and glucosuria without ketonuria. Mortality in children has been high (24%). This paper reports the case of a 14-month-old girl with Down's syndrome. Clinical and therapeutic as well as pathogenetic aspects are discussed.
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PMID:[Hyperosmolar nonketotic diabetic coma in children]. 15 87

The idea that the gene(s) that cause diabetes mellitus can be expressed in extrapancreatic cells has been examined by tissue culture techniques. Skin biopsies were obtained from 25 normal subjects (N), 26 overt diabetics (D), 16 of juvenile onset (JOD) and 9 of maturity onset (MOD), and 21 subjects genetically predisposed to diabetes (P) on the basis of maturity-onset diabetes in both parents. Each biopsy was subdivided, multiple skin fragments were explanted in vitro, and several parameters of cellular outgrowth were monitored in primary and secondary cultures until cell division ceased because of senescence. In general, the rank order of growth vigor was N greater than P greater than D although differences were often marginal and statistically significant between N and JOD and(or) MOD. Outgrowth of epithelial cells was more vigorous in N explants in early stages, but later, JOD and MOD cells grew better than those of N. Outgrowth of fibroblast cells from N explants was more vigorous both at early and later stages and required less time to achieve maximum percent outgrowth. In secondary cultures, N cells grew faster than the other three groups so that fewer days elapsed between subcultures but significant differences were only seen between N and one or two of the other groups over some of the first seven subcultures. The onset of cellular senescence occurred earlier in P and JOD cultures both in mean population doublings and calendar time. N cultures had a higher percent surviving clones after picking than MOD, and a shorter recloning time than clones of JOD. The replicative life-spans of cultures (mean population doublings +/- SE) were N = 52.54 +/- 2.24, P = 47.84 +/- 2.43, JOD = 47.12 +/- 2.99, and MOD = 46.40 +/- 4.04, but differences did not reach significance for N vs the other three groups. The data demonstrate that cellular growth is impaired in both JOD and MOD types of cultures and to a generally lesser extent in P cultures. This is consistent with intrinsic genetic defects but the possibility that persistent deleterious effects of in vivo pathophysiology contribute alone or in combination cannot be ruled out. Therefore, the diabetic defect(s) can be expressed in extrapancreatic cells of mesenchymal origin. This system should prove useful in exploring the interplay between genetic and environmental factors in diabetes, the mechanisms(s) of hyperglycemia and other metabolic derangements, and the propensity that affected individuals have to develop degenerative diseases.
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PMID:Diabetes mellitus and genetic prediabetes. Decreased replicative capacity of cultured skin fibroblasts. 42 58

We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (plus or minus SE) steady-state plasma glucose level of the 14 diabetic patients was 350 plus or minus 16 mg/100 ml, while that of 12 normal subjects was 121 plus or minus 4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion. Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
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PMID:Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. 111 64

1. In 161 consecutive cases of fluctuant hearing loss and 13 control cases of other causes of deafness, patients were examined for their ability to metabolize a 100 gm. oral dose of glucose. 2. The plasma glucose level in response to the oral dose of glucose was measured at hourly intervals for three hours. 3. Insulin and proinsulin levels were measured in 46 cases of fluctuant hearing loss and in 13 control cases. 4. None of the control group showed borderline or diabetic tolerance curves. 5. Fourteen per cent of the patients with fluctuant hearing loss had borderline glucose intolerance curves and 19 per cent showed diabetic glucose tolerance curves. 6. In patients whose insulin and proinsulin levels were determined, the insulin response to an oral glucose load was typical of adult onset diabetes, i.e., delayed hyperinsulinemia with concomitant hyperglycemia. The hyperinsulinemia was not associated with hyperproinsulinemia. 7. We conclude that in patients with fluctuant hearing loss there is a significantly higher incidence of borderline or diabetic glucose tolerance than in the "control deafness" or "normal population" group.
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PMID:Diabetes mellitus in fluctuant hearing loss. 115 1

High-performance liquid chromatographic (HPLC) analysis of human serum albumin (HSA) on Asahipak GS-520H columns at neutral pH (6.87) showed a clear resolution of human mercaptalbumin (HMA) and nonmercaptalbumin (HNA), which are reduced and oxidized form of HSA, respectively. We studied the conversion of HMA to HNA (mercapt-nonmercapt conversion) as an index of oxidative change of the tissues and organs in 28 normal subjects and in a total of 47 patients with non-insulin dependent diabetes mellitus (NIDDM). Mean (+/- SD) values of the HMA fraction of HSA, f(HMA), [HMA/(HMA + HNA)], was significantly lower in NIDDM patients than in normal subjects (0.63 +/- 0.067 vs 0.75 +/- 0.028, P < 0.001). It was lower in poorly controlled NIDDM patients (0.63 +/- 0.058, n = 20) than in well controlled NIDDM patients (0.67 +/- 0.032, n = 9) (P < 0.05). Plasma glucose values sampled on occasions including overnight fasting and postprandial ones (r = -0.441, n = 47, P < 0.01), but not plasma glucose values sampled on overnight fasting (r = -0.345, n = 29) or postprandial (r = -0.467, n = 18) conditions and HbA1c (r = -0.211, n = 34), negatively correlated with the f(HMA) values, indicating that mercapt-nonmercapt conversion may not be due to cumulative hyperglycemia over a month, but due to short-term alteration in blood glucose level. The presence or absence of diabetic complications including nephropathy, retinopathy and neuropathy did not affect the f(HMA) values. In conclusion, decreased f(HMA) values in the diabetic patients suggested the presence of a rapidly altered oxidative change of albumin due to hyperglycemia.
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PMID:Increased oxidized form of human serum albumin in patients with diabetes mellitus. 128 16

Besides insulin secretion, insulin sensitivity plays a key role in the feedback glucose-insulin closed loop. It can be altered in numerous physiological, pathological and pharmacological conditions. It can be estimated in vivo using methods that open the feedback loop (insulin suppression test, glucose clamp) or that analyze the closed loop by employing mathematical models of glucose kinetics. The most popular method is the euglycemic hyperinsulinemic glucose clamp. This test should be ideally coupled with a priming-constant infusion of a glucose tracer together with indirect calorimetry. This combination allows to study the glucose kinetics (Ra and Rd, and thus endogenous-mainly hepatic-glucose production) and its metabolism (oxidation or storage as glycogen), respectively. One alternative approach is the frequently sampled intravenous glucose tolerance test where the dynamic changes in plasma insulin and glucose levels are analyzed using the so-called 'minimal model' method. Noninsulin-dependent or type 2 diabetes is characterized by a significant defect in both insulin secretion and action. The insulin resistance is located at the liver site (increased glucose production) and at the peripheral tissues (decreased oxidation and, even more, defective storage of glucose in the muscles). This insulin resistance, which predominates at the postreceptor level, seems to be genetically determined but is worsened by weight excess and by hyperglycemia itself. This contributes to a vicious circle which aggravates progressively the severity of the disease.
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PMID:Assessment of insulin resistance in vivo: application to the study of type 2 diabetes. 130 10

Insulin resistance syndromes are heterogeneous in either severity or mechanism. Many drugs have been shown to counteract various elements of insulin resistance. Some of them, by normalization of metabolic parameters, decrease insulin resistance induced by chronic hyperglycemia in diabetes. Insulin and, to some extent, sulfonylureas are in this group, but these drugs are not stricto sensu medication of insulin resistance. Some drugs sensitize peripheral tissues to the action of insulin. For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin. Other compounds as vanadate or IGF-1 mimic some peripheral action of insulin. Finally, blockade of FFA oxidation by specific inhibitors (methylpalmoxyrate) can limit insulin resistance. In 1992, among these compounds, specific of insulin resistance, biguanides are mostly used. However, the efficacy of these drugs is moderate and limited to type 2 diabetes.
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PMID:Pharmacological approach in the treatment of insulin resistance. 130 17

To investigate the role of glucagon in the pathogenesis of diabetes, we observed change of plasma glucagon concentrations during glucose loading in normal subjects and patients with impaired glucose tolerance (IGT) and non-insulin dependent diabetes mellitus (NIDDM) using specific radioimmunoassay. The results showed that the fasting plasma glucagon levels in patients with IGT and NIDDM were similar to those of the normal subjects. The nadir of plasma glucagon level in the normal control occurred at 1-h after glucose loading and the changes of glucagon, glucose and insulin levels synchronized; but peaks of plasma glucose and insulin levels in the IGT and NIDDM patients were delayed at 2-h after glucose loading with the lowest glucagon level at 3-h. It was suggested that there were relative hyperglucagonemia and decrease of sensitivity of islet A cell to glucose in IGT and NIDDM patients. The present study also showed that hyperglucagonemia is related to the reduction of insulin secretion and might play an important role in the development of postprandial hyperglycemia in NIDDM.
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PMID:[Changes in plasma glucagon concentration in patients with diabetes mellitus and its clinical significance]. 132 51

Conflicting evidence has been reported on the metabolic fate of glucose following oral ingestion. We measured the metabolic pattern of gluconeogenic substrates as alanine, predominantly produced by muscle, and lactate after an oral glucose load in ten normal subjects and in eighteen non-insulin dependent diabetes mellitus (NIDDM) subjects. Neither in normal or NIDDM subjects were significant increases in plasma alanine observed, whereas a significant increase in plasma lactate was observed at 60, 90 and 120 min after a glucose load. Although a similar behaviour in plasma alanine and lactate between normal and NIDDM subjects was found, in NIDDM significantly higher levels of plasma alanine and lactate were found at each time. From these observations we conclude: 1) when glucose is ingested under post-absorptive conditions, since plasma alanine levels do not change concurrently with lactate increase, muscle tissue does not play a predominant role in glucose disposal 2) after an oral glucose load, the pattern of gluconeogenic precursors (alanine and lactate) is similar in normal and NIDDM subjects 3) the main cause of fasting and post-prandial hyperglycemia in NIDDM subjects may be due to an overproduction of alanine as well as lactate.
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PMID:Plasma alanine and lactate concentrations following glucose ingestion in normal and NIDDM subjects. 134 5


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