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

Insulin resistance, characterized by reduced responsiveness to normal circulating levels of insulin, leads to hyperglycemia and hyperinsulinemia resulting in a deadly quartet of non-insulin dependent diabetes mellitus, obesity, hypertension and dyslipidemia These complications, also referred to as 'Syndrome X' have been associated with an increased risk of coronary heart disease. A number of non-pharmacological and pharmacological interventions are available for prevention and treatment of insulin resistance. However, introduction of thiazolidinediones, the new orally active class of drug, has proved to be a major breakthrough in this field. These agents have been shown to reduce insulin resistance by a novel mechanism of action. By interacting with a family of nuclear receptors known as peroxisome proliferator activated receptors thiazolidinediones are thought to enhance the actions of insulin, thereby increasing insulin dependent glucose disposal and reducing hepatic glucose output. A series of animal and clinical studies in patients with impaired Glucose Tolerance and NIDDM have demonstrated the safety and effect of various thiazolidinediones including ciglitazone, pioglitazone and troglitazone. Thus, thiazolidinediones by unlocking insulin resistance act as a key to glycemic control and hence are likely to prove a useful and rational therapy in NIDDM and possibly other disorders resulting from insulin resistance.
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PMID:Thiazolidinediones--the new insulin enhancers. 1005 51

The notion that tissue resistance to insulin might play an important role in certain disease states is approximately 60 years old. However, recognition of its central role in this regard is a relatively recent phenomenon. In this review an effort has been made to trace a brief history of insulin resistance from its inception to its current position as the fundamental abnormality in both type 2 diabetes and Syndrome X.
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PMID:Insulin resistance and human disease: a short history. 1021 44

Severe obesity, defined as a body mass index > or = 35 kg/m2, is frequently associated with various biological abnormalities, particularly in the presence of intra-abdominal adiposity. The most important disorders belong to the so-called insulin resistance syndrome, metabolic syndrome or syndrome X: hyperinsulinaemia, impaired glucose tolerance or type 2 diabetes, dyslipidaemias, hyperuricaemia, hyperfibrinogenaemia. All these metabolic abnormalities are considered as cardiovascular risk factors. They are also correlated with the severity of the liver steatosis which is commonly observed in individuals with severe obesity. We report our experience of the evolution of these metabolic abnormalities after a marked weight loss induced by gastroplasty. We will analyse the favourable effects of bariatric surgery on insulin sensitivity, biological components of the metabolic syndrome, type 2 diabetes and liver steatosis.
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PMID:[How I treat ... an individual with severe obesity and metabolic abnormalities with gastroplasty]. 1032 Nov 1

The purpose of this investigation was to determine the prevalence and correlates of abnormal urinary albumin excretion and to examine the possible additive effects of cardiovascular risk factors on urinary albumin excretion in African Americans with type 2 diabetes mellitus. One hundred fifty-one African-American subjects who met WHO criteria for type 2 diabetes were included in this cross-sectional analysis. Subjects were identified through computerized medical records from a family medicine clinic and a community health center. Urinary albumin excretion ratios (UAER) were determined from overnight samples. The prevalence of abnormal urinary protein excretion was 51%. Of those with abnormal protein excretion, 36% had microalbuminuria and 15% had macroalbuminuria. Diabetes duration, waist to hip ratio, blood pressure, and total- and LDL cholesterol were significantly higher in subjects with macroalbuminuria. Regression analysis indicated that mean arterial blood pressure, diabetes duration and total cholesterol were independently associated with UAER. Mean UAER significantly increased with the addition of one or more syndrome X risk factors to pure diabetes. Our results indicate that African Americans with type 2 diabetes mellitus have a high prevalence of abnormal urinary protein excretion, which is associated with a clustering of additional cardiovascular risk factors. The fact that this increased risk was associated with hypertension indicates that screening for albuminuria in this population is essential and that a majority of African Americans with diabetes may be at risk for developing cardiovascular complications.
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PMID:Abnormal urinary protein excretion in African Americans with type 2 diabetes mellitus. 1035 70

Individuals with type 2 diabetes mellitus (n = 105; age 36-71 years) on diet therapy alone, and with quite good glycaemic control (mean HbA1c approximately 7.0%) were randomized to receive acarbose (100 mg three times daily) or placebo for 16 weeks, and changes in clinical and metabolic parameters indicative of Syndrome X were monitored. Fasting levels of glucose, glycosylated haemoglobin (HbA1c), true insulin, proinsulin, fibrinogen and lipids were measured four times weekly, and glucose, insulin, proinsulin and triglyceride responses to a standardized 1.6 MJ breakfast were determined at 0, 1 and 2 h post meal. Analysis was on an intention-to-treat basis. Fasting levels of glucose (P < 0.0001), triglycerides (P = 0.03) and HbA1c (P = 0.003) were reduced by acarbose over the 16 weeks of treatment. The mean change in HbA1c from week 0 to 16 differed by 0.4% (P = 0.003) between the two groups. Insulin (P = 0.06), proinsulin (P = 0.07) and glucose (P < 0.0001) responses to the standard meal were reduced. These data show that acarbose reduces fasting glucose and triglyceride levels, lowers HbA1c and limits the glycaemic and insulin response to food in individuals with type 2 diabetes mellitus with Syndrome X. Pharmacological agents that improve the metabolic environment and reduce insulin resistance have the potential to limit the progression of atherogenesis associated with type 2 diabetes mellitus.
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PMID:Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus? 1036 27

Metformin has been used for over 40 years as an effective glucose-lowering agent in type 2 (noninsulin-dependent) diabetes mellitus. Typically it reduces basal and postprandial hyperglycaemia by about 25% in more than 90% of patients when either given alone or coadministered with other therapies including insulin during a programme of managed care. Metformin counters insulin resistance and offers benefits against many features of the insulin resistance syndrome (Syndrome X) by preventing bodyweight gain, reducing hyperinsulinaemia and improving the lipid profile. In contrast to sulphonylureas, metformin does not increase insulin secretion or cause serious hypoglycaemia. Treatment of type 2 diabetes mellitus with metformin from diagnosis also offers greater protection against the chronic vascular complications of type 2 diabetes mellitus. The most serious complication associated with metformin is lactic acidosis which has an incidence of about 0.03 cases per 1000 patients years of treatment and a mortality risk of about 0.015 per 1000 patient-years. Most cases occur in patients who are wrongly prescribed the drug, particularly patients with impaired renal function (e.g. serum creatinine level > 130 micromol/L or > 1.5 g/L). Other major contraindications include congestive heart failure, hypoxic states and advanced liver disease. Serious adverse events with metformin are predictable rather than spontaneous and are potentially preventable if the prescribing guidelines are respected. Gastrointestinal adverse effects, notably diarrhoea, occur in less than 20% of patients and remit when the dosage is reduced. The life-threatening risks associated with metformin are rare and could mostly be avoided by strict adherence to the prescribing guidelines. Given the 4 decades of clinical experience with metformin, its antihyperglycaemic efficacy and benefits against Syndrome X, metformin offers a very favourable risk-benefit assessment when compared with the chronic morbidity and premature mortality among patients with type 2 diabetes mellitus.
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PMID:A risk-benefit assessment of metformin in type 2 diabetes mellitus. 1039 66

Insulin resistance, a smaller than expected response to a given dose of insulin, is associated with many common diseases including, ageing, polycystic ovarian disease, syndrome X, cancer, infections, trauma and, most significantly, obesity and type 2 diabetes mellitus. The biochemical basis of insulin resistance in type 2 diabetes has been the subject of many studies. Earlier studies have indicated that quantitative regulation of the insulin sensitive glucose transporters (Glut-4) and insulin receptors themselves may contribute to this disorder, however, these two factors are probably inadequate to explain the extent of insulin resistance. This point also became apparent by the development of only mild hyperinsulinaemia in mice with a targeted mutation in the Glut-4 gene. Studies on postreceptor defects in type 2 diabetes has recently focused on the intrinsic catalytic activity of the insulin receptor and downstream signalling events. A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes. Importantly, this appears to occur in all of the major insulin-sensitive tissues, namely the muscle, fat and liver. It is now clear that decreased signalling capacity of the insulin receptor is an important component of this disease. I will review some of the potential mechanisms underlying this deficiency.
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PMID:The role of TNFalpha and TNF receptors in obesity and insulin resistance. 1039 91

The prevalence of obesity has increased over the past three decades, in children as well as in adults. When obesity develops in the childhood years, excess adiposity generally continues into adult years, and adult obesity with childhood onset is frequently more severe. The health consequences of obesity in adults are well established, including greater rates of hypertension, non-insulin dependent diabetes mellitus, and heart disease. This paper will discuss the risk factors for these adult disorders that are detectable in obese children. Compared to normal weight children, obese children have higher blood pressure, higher plasma insulin levels, and a more atherogenic lipid pattern. Thus, the characteristic features of Syndrome X, or the insulin resistant syndrome, can be detected in obese children and adolescents. The vascular consequences of exposure to these metabolic risk factors beginning in childhood have yet to be completely determined. However, it is very likely that childhood obesity does contribute significantly to cardiovascular disease. For these reasons, greater efforts should be mounted to reduce the currently rising rates.
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PMID:Obesity and other risk factors in children. 1042 Oct 92

It has been increasingly recognised in recent years that type 2 (non-insulin-dependent) diabetes is part of a cluster of cardiovascular risk factors known as the metabolic syndrome, but also endorsed with such names as the deadly quartet, syndrome X and the insulin resistance syndrome. Atherosclerosis is the most common complication of type 2 diabetes among Europeans, and coronary artery, cerebrovascular and peripheral vascular disease are 2 to 5 times more common in people with this condition than in those without diabetes. These observations indicate that the treatment of type 2 diabetes requires agents that do more than simply lower blood glucose levels, and a therapy with both antihyperglycaemic effects and beneficial effects on dyslipidaemia, hypertension, obesity, hyperinsulinaemia and insulin resistance is likely to be most useful. In this respect, metformin has an important and established role: this drug has been shown to lower blood glucose and triglyceride levels, and to assist with weight reduction and to reduce hyperinsulinaemia and insulin resistance. Studies in the Israeli sand rat, Psammomys obesus, have indicated hyperinsulinaemia/insulin resistance to be the initial and underlying metabolic disorder in obesity and type 2 diabetes. Thus, the well established effect of metformin in reducing insulin resistance makes this drug an excellent candidate for the prevention of progression of impaired glucose tolerance to type 2 diabetes, and for the reduction of mortality associated with cardiovascular disease.
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PMID:Clinical efficacy of metformin against insulin resistance parameters: sinking the iceberg. 1057 21

Measurements have been made, in adult male diabetic patients and control subjects, of the urinary content of inositol phosphoglycans (IPGs), the IPG A-type and IPG P-type forms, which, among other actions, regulate pathways of glucose utilization, lipogenesis, triglyceride formation, and pyruvate dehydrogenase (PDH) activity. Urine samples from the entire diabetic group showed a 2- to 3-fold increase in IPG A-type, and a fall in the IPG P-type:IPG A-type ratio relative to the control group. Subdivision of the diabetic patients into lean IDDM and obese NIDDM groups revealed significant differences in the IPG P-type:IPG A-type ratio between these groups, this ratio decreasing with increases in the body mass index (BMI). Analysis of the relationships among IPGs and HbA1, blood pressure, and BMI indicated that a fall in the IPG P-type:IPG A-type ratio correlated with a rise in the HbA1 (indicative of impaired glycemic control), with increased systolic blood pressure and increased obesity, all factors linked to Syndrome X. There was a parallism between the profile of the IPG P-type:IPG A-type ratio and the well-established pattern of insulin resistance and BMI. In vitro studies of the effects of alterations in the IPG P-type:IPG A-type ratio on the activation of the pyruvate dehydrogenase complex (PDH complex) at the PDH phosphatase reaction demonstrated that IPG A-type forms antagonized the stimulation of the PDH phosphatase by IPG P-type forms, thus having a negative effect on the conversion of PDH to the active, dephosphorylated, form. This observation could provide a mechanism whereby the shifts in the IPG P-type:IPG A-type ratio reported above could change the metabolic pattern from one directed to glucose oxidation to one more directed toward energy conservation and lipid storage.
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PMID:Inositol phosphoglycans in diabetes and obesity: urinary levels of IPG A-type and IPG P-type, and relationship to pathophysiological changes. 1060 79


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