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

Acanthosis nigricans is a skin lesion characterized by thickening and apparent darkening of the keratin layer of the skin, usually on the neck and axillae. Recent studies reveal that this disorder is directly associated with hyperinsulinemia. A major implication of hyperinsulinemia is insulin resistance--a primary factor in the development of type II diabetes mellitus. Prolonged hypersecretion of insulin presumably leads to pancreatic exhaustion and subsequent glucose intolerance that can progress to type II diabetes. Prospective studies of individuals with acanthosis nigricans have shown very high prevalence rates of type II diabetes. Prevalence studies among adolescents have shown that the lesion appears early in life and is a common finding in some ethnic groups. These data suggest that acanthosis nigricans is an easily detected empirical marker for elevated risk of type II diabetes. The lesion can appear long before the onset of glucose intolerance. Thus, including acanthosis nigricans screening in a comprehensive disease-prevention program can help identify people at risk for type II diabetes prior to the actual onset of glucose intolerance, as well as individuals with undiagnosed diabetes. Interventions that reduce insulin resistance include weight loss and regular physical activity.
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PMID:Assessment of patients with acanthosis nigricans skin lesion for hyperinsulinemia, insulin resistance and diabetes risk. 154 62

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.
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PMID:The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy. 163 93

Despite intensive research effort, the aetiology of non-insulin dependent diabetes mellitus remains unknown. In this disorder, hyperglycaemia results from three defects: impaired suppression of hepatic glucose production; reduced peripheral clearance of glucose; and impaired glucose-mediated insulin secretion. It has been proposed that reduced peripheral glucose clearance is the primary or inherited defect and that hyperinsulinaemia secondary to this eventually leads to beta cell exhaustion and impaired insulin secretion. Other authors have proposed that the initial defect is an abnormality in the first phase of insulin secretion. In this paper it is proposed that the primary abnormality is failure of hepatic gluconeogenesis to suppress adequately and that the resulting excess glucose flux results in peripheral insulin resistance and in a defect of glucose-mediated insulin secretion. This hypothesis is supported by recent data showing the glucose per se can induce defects in insulin action and insulin secretion.
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PMID:The aetiology of non-insulin-dependent diabetes mellitus: is abnormal suppression of hepatic gluconeogenesis the primary event? 194 65

In this study, in vitro B-cell models are described, which may be applicable for studying the reported B-cell desensitization produced by hyperglycemia in IDDM and NIDDM. Using a programmable perifusion/perfusion system, insulin secretion from perifused islets was measured at 10-30-min intervals for 24-50 h. After 3-4 h continuous glucose (11 mM), a new phase of insulin release occurs in which secretion declines to, and remains at, approximately 25% maximal release. Results were similar when using: perifused islets embedded in Cytodex 3, or Bio-Gel P-2, 100-200 mesh; batchincubated islets with hourly changes of medium; and the isolated pancreas perfused for 8 h. Three different media, Hana HB 104 (fortified, fully defined medium), RPMI-1640 + 10% FBS, and perfusion bufferalbumin, were used. Despite reduced secretion to continuous glucose, each system responded vigorously to an acute stimulation with glucose-forskolin. Decreased secretion was primarily caused by decreased secretagogue efficiency (reduced fractional secretion). Prolonged stimulation with glucose or glucose-IBMX produced a similar waning of secretion regardless of the amount of insulin released. It is concluded that the third phase of insulin secretion may represent a secret-agogue-induced, signal desensitization of the B-cell, rather than exhaustion of a B-cell compartment of stored insulin.
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PMID:The third phase of in vitro insulin secretion. Evidence for glucose insensitivity. 351 47

To elucidate the pathogenesis of diabetes in spontaneously diabetic Chinese hamsters (CHAD strain), a longitudinal study from just after weaning to overt diabetic state was performed. Fasting and non-fasting plasma glucose, non-fasting plasma insulin and pancreatic hormone contents (insulin, glucagon and amylin) were measured, and light microscopic examination of pancreatic islets by immunohistochemical technique and pancreas perfusion study were performed. No insulitis was found in the islets of the CHAD strain. In animals aged 1 month, there was no significant difference in the percentage of B-cell area to islet area between the CHAD strain and the control. At this stage, hyperinsulinemia was observed despite normal plasma glucose levels both in fasting and non-fasting states. In the animals of the CHAD strain aged 2-4 months, insulin secretion from the pancreas, pancreatic insulin content and non-fasting plasma insulin level decreased in proportion to the decrease of B-cell mass. In animals aged about ten months, severe hyperglycemia and hypoinsulinemia were observed. We demonstrated the existence of amylin-like immunoreactivity in the B-cells of Chinese hamsters. However, no amyloid deposit was observed in the islets of the CHAD strain. After the onset of diabetes, amylin secretion from the pancreas and pancreatic amylin content in the CHAD strain were significantly lower than those in the control. We demonstrated the natural history of B-cell dysfunction in the CHAD strain. It could mean the process of B-cell exhaustion. The profile of the CHAD strain is similar to some types of human NIDDM. Therefore, the CHAD strain is a useful diabetic model in the study of NIDDM.
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PMID:Natural history of B-cell dysfunction in spontaneously diabetic Chinese hamsters. 798 44

This study determined the effects of exercise on the ability of inflammatory macrophages to inhibit tumor cell growth in vitro (macrophage cytotoxicity). Thioglycollate injection (1 ml ip) was used as an inflammatory challenge and to partially activate macrophages for cytotoxicity. Inbred male C3H/HeN mice (n = 180) exercised moderately (MOD, 18 m/min, 30 min/day, 5% grade) or to exhaustion (EXH, 18-35 m/min, 2-4 h, 5% grade) on a motor-driven treadmill for 3 consecutive days after injection. Control (CON) mice were kept in stimulated treadmill lanes directly over the runners. Mice were killed immediately or 3 or 8 h postexercise. Macrophages from both MOD and EXH exercise groups manifested significantly (P < 0.05) enhanced (approximately 50%) cytotoxicity compared with those from CON group at all time points postexercise. This potentially beneficial exercise effect was not related to macrophage production of interleukin-1 beta, reactive nitrogen or oxygen intermediates, or number of macrophages in the assay but may have been manifested, in part, by tumor necrosis factor-alpha. Plasma corticosterone was significantly elevated immediately postexercise in MOD and EXH compared with CON mice; however, no evidence existed for an immuno-suppressive effect of corticosterone on macrophage cytotoxicity, perhaps because of insensitivity of inflammatory macrophages to glucocorticoid suppression seen in vitro. These data only partially support the "inverted U hypothesis," which states that moderate exercise may enhance, whereas very heavy exercise or a lack of exercise may attenuate, the immune response. Further study is needed to determine the physiological significance of these findings and the effects of exercise on macrophage subsets sensitive to glucocorticoid suppression (i.e., fully activated macrophages).
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PMID:Exercise increases inflammatory macrophage antitumor cytotoxicity. 822 94

Insulin action is highly likely to be primarily genetically determined (given a permissive or facilitative environment, for example sufficient calorie availability), as shown by variations in ethnic distribution, evidence for familial transmission and genotypic responses to experimentally induced metabolic stresses. Further, it is likely that the genetic predisposition to insulin resistance is closely linked to (or perhaps synonymous with) the predisposition to develop overt NIDDM. Alternatively, in the development of diabetes, the genetic basis for insulin resistance may be necessary, but not sufficient, requiring a second major gene for beta-cell vulnerability (e.g. exhaustion, deterioration of function, amyloid deposition). The future examination of the genetics of insulin action depends in large measure on the method of assessment of insulin action that is selected and its consistent application to individuals, families and populations. The phenomenological approaches currently being used to describe and define insulin resistance could be identifying many different disorders, all leading to an apparent decrease or impairment of insulin action compared with that in 'normals'. Selection of any method for determining the presence of insulin resistance, together with selection of the threshold for 'present versus absent' is, at best, difficult. It is further complicated by the frequent association of insulin resistance with a wide range of disturbances, including hypertension, dyslipidaemia and glucose intolerance--the insulin resistance 'syndrome'. A number of possible loci and candidate genes controlling insulin action have been studied, and most have been ruled out as the probable underlying cause of the majority of cases of defective insulin action. Among those genes that are unlikely to be determinants of insulin resistance (except in a few rare cases of mutations) are those for insulin, the insulin receptor, glucose transporters and the genes for many specific enzymes. While these are unlikely to be responsible for insulin resistance, such potential genetic defects cannot be fully excluded using present methods. Direct gene sequencing of polymerase-chain-reaction amplified DNA may be the ultimate approach to identifying the critical defects underlying insulin resistance. Other candidate genes regulating insulin action are likely soon to come forth, such as those controlling the generation and function of the intracellular mediators of insulin action.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetics of insulin action. 830 12

Most of diabetics have no symptoms and chemical analyses may be sole way to diagnose the disease itself and its complications. Chemical analyses are also important to assess the propriety of glycemic control during every possible treatment of diabetes. Some markers for long-term glycemic control other than glucose concentration may be also used as a screening methods for glucose intolerance. HbA1c is established for long term as a marker for glycemic control but still large interlaboratory variation is present. Fructosamine is measured by a simpler procedure but many deoxidizing materials in serum especially superoxide may interfere with the reaction. Glycated albumin should be more reliable than fructosamine but a standard method of measurement has not been established yet. The decrease in serum 1,5-anhydro-D-glucitol(1,5-AG) is very sensitive to urinary glucose excretion and may be useful as a marker of glycemic control and diagnosis of diabetes. Discrimination of Type I(IDDM) from Type II(NIDDM) in Japanese diabetic patients is sometimes very difficult and evidences of autoimmunity by anti-glutamic acid decarboxylase(GAD) antibody and of exhaustion of insulin secretion by C-peptide measurement 6min after combined infusion of 1mg of glucagon and 20ml of 50% glucose are the few methods to diagnose. Early diagnosis of diabetic complication is another important point of clinico-chemical determinations. Usually, each diabetic complication progresses in parallel. Micro-measurement of urinary transferrin is one of the most sensitive methods likewise urinary microalbumin measurement. Future measurement of advanced glycation end product (AGE) may also tell us if patients are suffering from diabetic complications or if one is suffering from diabetes or not.
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PMID:[Recent progress in diagnoses of diabetes and its complications]. 856 34

Longitudinal changes in serum insulin concentrations in relation to the natural history of glucose intolerance and factors associated with the incidence of NIDDM were studied in 838 nondiabetic Micronesian Nauruans over the 5.1-year period from 1982 to 1987. In 13 individuals who had data at three time-points and who developed NIDDM only at the final test, 2-h insulin levels followed an inverted V-shaped pattern as glucose tolerance declined to NIDDM. Subjects who were normal (n = 651) or had impaired glucose tolerance (IGT) (n = 187) at the 1982 baseline survey were divided into six natural history categories depending on glucose tolerance in 1987. Changes in glucose tolerance were accompanied by changes in mean 2-h insulin concentration that paralleled the inverted V pattern seen in the 13 individuals. Longitudinal changes in fasting insulin were less consistent, but mean levels increased as subjects developed NIDDM. The 5.1-year incidence of NIDDM was strongly related to baseline fasting and 2-h glucose concentrations, but associations with insulin levels were weak and inconsistent. Neither fasting nor 2-h insulin concentrations contributed to logistic regression models predicting deterioration in glucose tolerance, whereas fasting and 2-h glucose levels were included in all models and BMI also predicted deterioration from normal. These data showing sequential changes in insulin concentrations support the beta-cell exhaustion theory of NIDDM pathogenesis. However, in contrast to glucose concentrations and obesity, insulin levels are poor predictors of NIDDM risk in Nauruans. This reflects the complexity of interactions with other metabolic markers and the inability of a single examination to characterize the point along the inverted V curve of insulin secretion that an individual has reached.
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PMID:Insulin levels and the natural history of glucose intolerance in Nauruans. 882 73

Refractoriness of the pancreatic beta-cell to glucose stimulation plays a role in the secretory defect of NIDDM, but the mechanisms underlying this refractoriness are not clear. The purpose of this study was to determine whether the HIT-T15 pancreatic beta-cell line can be used as an investigative model for refractoriness of glucose-induced insulin secretion and, if so, whether the mechanism for this refractoriness involves alteration in stimulus-secretion coupling (desensitization) or results from exhaustion of insulin stores. In perifusion experiments, acute insulin responses (AIRs) in HIT-T15 cells progressively diminished during consecutive 5-min glucose (11.1 mmol/l) pulses (G) given every 20 min (G1=9.2+/-1.3, G2=4.1+/-1.0, G3=2.7+/-0.7, G4=2.5+/-1.1 microU/ml). To determine whether this refractoriness for glucose extended to the potentiating effects of glucose on nonglucose secretagogues, cells were challenged with arginine after desensitization with glucose. In HIT-T15 cells, the response to the arginine pulse (16.7+/-5.2 microU/ml) after three glucose pulses was significantly less (P < 0.01) than the response to a control arginine pulse (29.6+/-12.1 microU/ml) preceded by an infusion of buffer in the absence of glucose pulses. Variable rest periods after desensitization allowed recovery of the AIR in HIT-T15 cells; responses 30, 60, 90, and 120 min after the desensitization procedure increased in a stepwise fashion (3.8+/-2.7, 4.5+/-2.7, 7.8+/-5.2, and 9.7+/-5.3 microU/ml, respectively). To differentiate desensitization from exhaustion of insulin stores, studies were performed in the presence of epinephrine, a potent inhibitor of insulin secretion. In HIT-T15 cells, after three pulses of glucose during the epinephrine infusion, epinephrine was discontinued and the insulin response to a fourth pulse was assessed. The G4 AIR (1.9+/-0.6 microU/ml) was markedly less than a control G4 AIR (5.4+/-1.2 microU/ml) that followed an epinephrine infusion alone with no concurrent glucose pulses. Beta-cell refractoriness was also induced in the HIT-T15 cell using 45-min steady-state infusions of glucose. Cells were exposed to a 45-min infusion of either 3.7 or 11.1 mmol/l glucose, rested for 20 min in the absence of glucose, and then challenged with a 5-min, 11.1 mmol/l glucose pulse. In both cases, the AIR to the 5-min pulse (10.2+/-5.1 and 2.9+/-1.4 microU/ml after the 3.7 and 11.1 mmol/l infusion, respectively) was lower than the AIR to a control pulse (27.4+/-5.9 microU/ml) not preceded by glucose infusion. These studies demonstrated that the HIT-T15 cell line is an appropriate model for studying mechanisms of beta-cell refractoriness to glucose signaling. The short-term intensive glucose stimulation paradigms used in our studies induced an abnormality in insulin secretion that is consistent with desensitization but not beta-cell exhaustion.
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PMID:Differentiation between glucose-induced desensitization of insulin secretion and beta-cell exhaustion in the HIT-T15 cell line. 956 94


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