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

Type 2 (non-insulin-dependent) diabetes mellitus is a progressive metabolic disorder arising from genetic and environmental factors that impair beta cell function and insulin action in peripheral tissues. We identified reduced diacylglycerol kinase delta (DGKdelta) expression and DGK activity in skeletal muscle from type 2 diabetic patients. In diabetic animals, reduced DGKdelta protein and DGK kinase activity were restored upon correction of glycemia. DGKdelta haploinsufficiency increased diacylglycerol content, reduced peripheral insulin sensitivity, insulin signaling, and glucose transport, and led to age-dependent obesity. Metabolic flexibility, evident by the transition between lipid and carbohydrate utilization during fasted and fed conditions, was impaired in DGKdelta haploinsufficient mice. We reveal a previously unrecognized role for DGKdelta in contributing to hyperglycemia-induced peripheral insulin resistance and thereby exacerbating the severity of type 2 diabetes. DGKdelta deficiency causes peripheral insulin resistance and metabolic inflexibility. These defects in glucose and energy homeostasis contribute to mild obesity later in life.
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PMID:Downregulation of diacylglycerol kinase delta contributes to hyperglycemia-induced insulin resistance. 1826 70

Breast feeding is the best way to nurture healthy newborns of healthy mothers. A number of studies have shown that breast feeding may protect against the later development of obesity and related metabolic diseases. Using data from our own meta-analysis as well as studies by other groups, in this review we systematically examine the current state of evidence regarding this topic. Breast feeding, in general, is shown to be associated later in a child's life with decreased risk of overweight, decreased blood cholesterol and blood pressure, and a reduced risk of developing type 2 diabetes. Additionally, we review data of our Kaulsdorf Cohort Study (KCS) showing, however, that these effects might be reversed when the mother is affected by a non-communicable disease such as diabetes mellitus, which alters the composition of breast milk. In particular, exposure to breast milk from diabetic mothers during the first days of life (first week; early neonatal period) seems to increase rather than decrease risk of overweight and, consecutively, impaired glucose tolerance in childhood. Taken together, current findings show clearly that breast feeding is effective in lowering the risk of developing key features of the metabolic syndrome in later life, and should therefore be promoted. With increasing prevalence of overweight and diabetes in women, however, more research is urgently needed to clarify whether breast feeding might even have negative consequences for risk of overweight and diabetogenic disturbances when the mother suffers from a metabolic disorder. From a more general perspective, breast feeding and its long-term consequences are an important paradigm for "perinatal programming" of health and disease.
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PMID:Breast feeding and the risk of obesity and related metabolic diseases in the child. 1837 Jul 91

Obesity is a chronic metabolic disorder that affects one third of American adults. Modest weight losses of just 5% to 10% of body weight, which are achievable with lifestyle modification and pharmacotherapy, can lead to remarkable improvements in many obesity-associated co-morbidities, including dyslipidemia, hypertension, and type 2 diabetes. In this review, the indications for pharmacotherapy and the goals of treatment are discussed, and current and future pharmacologic approaches to the treatment of obesity are examined. Current pharmacologic therapies for obesity are limited, but recent advances in our understanding of the complex and overlapping endocrine pathways that regulate body weight have led to new opportunities for antiobesity drug development. Important drug targets that are highlighted in this review include adipocyte-derived hormones, hypothalamic neuropeptides, and gastrointestinal hormones.
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PMID:Pharmacotherapy for obesity. 1837 85

Pancreatic beta cells secrete insulin when blood glucose levels are high. Dysfunction of this glucose-stimulated insulin secretion (GSIS) is partly responsible for the manifestation of type 2 diabetes, a metabolic disorder that is rapidly becoming a global pandemic. Mitochondria play a central role in GSIS by coupling glucose oxidation to production of ATP, a signal that triggers a series of events that ultimately leads to insulin release. Beta cells express a mitochondrial uncoupling protein, UCP2, which is rather surprising as activity of such a protein is anticipated to lower the efficiency of oxidative phosphorylation, and hence to impair GSIS. The mounting evidence demonstrating that insulin secretion is indeed blunted by UCP2 agrees with this prediction, and has provoked the idea that UCP2 activity contributes to beta cell pathogenesis and development of type 2 diabetes. Although this notion may be correct, the evolved function of UCP2 remains unclear. With this paper we aim to provide a brief account of the present state of affairs in this field, suggest a physiological role for UCP2, and highlight some of our own recent results.
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PMID:On the role of uncoupling protein-2 in pancreatic beta cells. 1843 13

Metformin is a biguanide commonly used in type 2 diabetes mellitus (DM). Lactic acidosis, a potentially life-threatening metabolic disorder, may be due to a number of different causes, including metformin therapy. We present a case of a severe metformin-induced lactic acidosis in a patient with type 2 DM, admitted to the emergency department with a history of dehydration due to diarrhoea and complicated by acute renal failure. Patient complained malaise and severe weakness and was tachypneic (Kussmaul's respiration), agitated and confused, with a Glasgow Coma Scale score of 13/15. Heart rate was 75 b/min and blood pressure 110/80 mmHg. The pH was 6.87, HCO3- 3 mmol/l, lactate 15 mmol/l, potassium 6.9 mEq/l. The renal function was markedly impaired with a creatinine of 9.75 mg/dl, and pancreatic enzymes, amylase and lipase, were also increased in absence of abdominal pain. Patient was treated with intravenous fluids, bicarbonate infusion and haemodialysis with bicarbonate buffered replacement fluid. Clinical conditions improved rapidly, with a progressive normalization of the acid-base balance and the other laboratory data. Authors discuss the pathophysiologic mechanisms of these alterations with particular regard to the role played by metformin as potential cause of lactic acidosis.
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PMID:Metformin-induced lactic acidosis in a type 2 diabetic patient with acute renal failure. 1846 66

Although type 2 diabetes has been traditionally understood as a metabolic disorder initiated by insulin resistance, it has recently become apparent that an impairment in insulin secretion contributes to its manifestation and may play a prominent role in its early pathophysiology. The genetic dissection of Mendelian and, more recently, polygenic types of diabetes confirms the notion that primary defects in insulin synthesis, processing and/or secretion often give rise to the common form of this disorder. This concept, first advanced with the discovery and physiological characterisation of various genetic subtypes of MODY, has been extended to other forms of monogenic diabetes (e.g. neonatal diabetes). It has also led to the identification of common risk variants via candidate gene approaches (e.g. the E23K polymorphism in KCNJ11 or common variants in the MODY genes), and it has been validated by the description of the robust physiological effects conferred by polymorphisms in the TCF7L2 gene. More recently, the completion and integration of genome-wide association scans for this disease has uncovered a number of heretofore unsuspected variants, several of which also affect insulin secretion. This review provides an up-to-date account of genetic loci that influence risk of common type 2 diabetes via impairment of beta cell function, outlines their presumed mechanisms of action, and places them in the context of gene-gene and/or gene-environment interactions. Finally, a strategy for the analogous discovery of insulin resistance genes is proposed.
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PMID:Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: where are the insulin resistance genes? 1850 48

Atherosclerotic diseases, such as myocardial infarction, are rising in incidence in Japan as well as in the Western countries, and postprandial metabolic disorders are drawing particular attention as a risk factor for their development. Again, it is known that there exist a population of patients whose fasting glucose and triglyceride levels are found to be within a normal range, but who present with hyperglycemia and hypertriglyceridemia postprandially, which has led to both postprandial hyperglycemia and hyperlipidemia becoming recognized as risk factors for cardiovascular disease. In recent years, there is a deepening of awareness that common pathological conditions underlying these diseases include visceral fat accumulation, insulin resistance, and decreased early insulin response, which can often be accounted for by the single concept of "postprandial metabolic disorders", which has important implications as an early therapeutic target for prevention of cardiovascular disease. Of note, it has been suggested that in early type 2 diabetes characterized by postprandial hyperglycemia, early insulin response is found to be decreased, often demonstrating a pattern of delayed and excessive insulin secretion (postprandial hyperinsulinemia), which is, in turn, often complicated by postprandial lipid metabolic disorder. In this paper, therefore, we would like to discuss how to evaluate, prevent and treat postprandial metabolic disorders in light of their pathological implications.
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PMID:[Postprandial metabolic disorder]. 1854 Mar 74

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is characterized by insulin resistance and hyperglycemia. Leptin inhibits the glucose-stimulated insulin secretion, and leptin receptors are present on beta cells as well as on fat cells, thus enabling leptin to modulate both insulin secretion and action. Therefore, leptin (LEP) and leptin receptor (LEPR) genes could play a role in the regulation of glucose and insulin after an oral glucose load. For the association study of LEP and LEPR with T2DM and metabolic traits, 752 women from Seoul National University Hospital (SNUH data) and 532 women from the Korean Health and Genome Study (KHGS data) were selected. Using the SNUH data, we identified that LEP-632G>A and +4998A>C polymorphisms were marginally associated with T2DM, LEP+4950G>A was significantly associated with several metabolic traits, and LEPR+5193G>A, +7187A>C, +27265G>A, +35861T>C, and +52289A>G showed strongly significant association with body mass index (BMI). We observed reproducibility of these results using the KHGS data; LEP+4950G>A and +4998A>C were significantly associated with systolic blood pressure and low-density lipoprotein cholesterol level, respectively. In conclusion, we observed that several polymorphisms in LEPR that had previous reports of association with BMI were significantly replicated in our samples and newly found that some variations of LEP were associated with T2DM and metabolic traits.
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PMID:Genetic variations in the leptin and leptin receptor genes are associated with type 2 diabetes mellitus and metabolic traits in the Korean female population. 1856 65

Type 2 diabetes mellitus is a metabolic disorder that results from defects in both insulin secretion and insulin action. Questions remain about when insulin therapy is indicated; thus, the aim of this study was to evaluate homeostasis model assessment beta-cell (HOMAbetacell) values as surrogate criteria for insulin therapy indication in patients with type 2 diabetes. A prospective study was performed involving 189 type 2 diabetic patients with deficient metabolic control assessed by clinical and laboratory parameters. All patients received nutritional intervention and combination therapy with metformin and glimepiride. Patients who did not respond were admitted to the next phase, which consisted of glimepiride + metformin + rosiglitazone oral therapy and revaluation after 3 months. Comparisons between responders and nonresponders in this phase were made in order to achieve differences in metabolic parameters and beta cell function. Of 189 patients studied, 150 (79.36%) were considered full responders in the first phase of this study. The remaining 39 patients were admitted in the second trial phase, in which 20 patients (51.28%) responded to triple oral therapy, while the other 19 (49.72%) required insulin therapy. Significant differences were found in fasting and postprandial glycemia (P < 0.001; P < 0.004) between the non-insulin-requiring group (200 +/- 12.0 mg/dL; 266.05 +/- 17,67 mg/dL) and the insulin-requiring group (291.5 +/- 17.6 mg/dL; 361.6 +/- 26.1 mg/dL). Likewise, significant differences were observed in homeostasis model assessment insulin resistance (HOMAIR) and HOMAbetacell values (P < 0.002; P < 0.04) between non-insulin-requiring patients (7.7 +/- 0.8; 24.5 +/- 1.3%) and insulin-requiring patients (12.6 +/- 1.2; 19.4 +/- 2.4%). Finally, significant differences were observed when comparing body mass index (non-insulin-requiring group, 29.2 +/- 0.4 kg/m, versus insulin-requiring group, 27.1 +/- 0.9 kg/m; P < 0.05). HOMAbetacell determination in clinical practice is a useful tool to determine when insulin therapy should be started for type 2 diabetic patients.
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PMID:Homeostasis model assessment (HOMA) as surrogate insulinization criteria in patients with type 2 diabetes. 1864 47

The troubling evolution of Type 2 Diabetes into epidemic proportions bearing dramatic consequences has generated significant interest leading to a strong research focus and therefore the subject of several studies in recent years. This article examines Type 2 Diabetes Mellitus and its complications on the basis of a literature review addressing their epidemiological situation on an international scale--including indigenous peoples--and their socio-cultural determinants. This study reveals important ethnic disparities in terms of mortality and morbidity, as well as the multi-factored origin of this metabolic disorder, most notably among indigenous populations. Above and beyond the limits of prevention programmes, this literature review addresses the importance of reinforcing ethnoepidemiological studies among vulnerable peoples in order to improve our understanding of the emergence and development of this particularly complex pathological phenomenon
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PMID:[Towards the development of an ethno-epidemiological study of type-2 diabetes and its complications]. 1869 10


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