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

The role of increases in basal glucose production (EGP) in the pathogenesis of hyperglycaemia in type 2 diabetes (DM2) has been controversial. It is proposed here that the differences arose from: (i) different patient populations at different stages in the evolution of the disease, (ii) a non-steady state due to diurnal variations in EGP, and measurements at different times of day, and (iii) differences in experimental techniques: tracers, priming strategies and methods of calculation. Methodologically we show that (i) non-steady-state methods and (ii) a one-compartment model with volume of distribution estimated from tracer data are necessary in DM2. Studies with sufficient data demonstrated diurnal variations in EGP, with the highest rates in the morning, normalizing by late afternoon. Metabolic clearance rate of glucose (MCR) remained constant. Long-standing DM2 demonstrated increases in glycaemia and relative decreases in morning EGP, probably feedback-induced. A falling MCR, partly secondary to glucotoxicity, likely induced the rise in baseline hyperglycaemia.
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PMID:Tracer-determined glucose fluxes in health and type 2 diabetes: basal conditions. 1296 89

Microalbuminuria is a marker for diabetic nephropathy. It also signifies cardiovascular disease, as well as nephropathy, in type 2 diabetes (DM2). Microalbuminuria may precede DM2, occurring with the insulin resistance syndrome and its components, including obesity and hypertension. Other indicators of cardiovascular risk, such as markers of inflammation, are associated with microalbuminuria in populations of patients with and without diabetes. With the rising prevalence of DM2 in minority youth, especially in Native Americans, a marker for future disease risk would allow earlier prevention strategies to be tested. Before microalbuminuria can be used in a prevention strategy, more needs to be known about the mechanism(s) of the association between elevated excretion, its relationship to glucose intolerance, and its relative contribution to cardiovascular and renal disease. These questions are especially applicable as we begin to observe the long-term complications of diabetes in youth.
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PMID:Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective. 1476 31

Because there is not an optimal control for Type 2 diabetes mellitus (DM2), which encompasses about 90% of diagnosed diabetic patients, its prevention is key. Early detection of DM2 development can be made through impaired fasting glucose and/or impaired glucose tolerance diagnosis. However, cases exist when oral glucose tolerance test (OGTT) results show an hyperglycemic peak >or =200 mg/dl as a unique alteration. This alteration is defined as impaired hyperglycemic peak (IHP) and should be considered as an additional early indicator of DM2 development. Because IHP is commonly misdetected by the standard OGTT, it is proposed that this misdetection can be solved using a closer sampled OGTT. The objective of this research was to detect IHP on 225 volunteers using a 10 min sampled OGTT during 2 h. Results show the existence of IHP in 25 cases, making it the most frequent and the less detected OGTT alteration. In eight of these cases, IHP could not have been detected using a standard OGTT, because at 30, 60 and 90 min, plasma glucose concentrations were <200 200 mg/dl, however, at 40, 50, 70, and/or 80 min, IHP exists.
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PMID:The impaired hyperglycemic peak as an additional indicator of Type 2 diabetes development is misdetected. 1496 38

The causes of cerebral accumulation of amyloid beta-protein (Abeta) in most cases of Alzheimer's disease (AD) remain unknown. We recently found that homozygous deletion of the insulin-degrading enzyme (IDE) gene in mice results in an early and marked elevation of cerebral Abeta. Both genetic linkage and allelic association in the IDE region of chromosome 10 have been reported in families with late-onset AD. For IDE to remain a valid candidate gene for late-onset AD on functional grounds, it must be shown that partial loss of function of IDE can still alter Abeta degradation, but without causing early, severe elevation of brain Abeta. Here, we show that naturally occurring IDE missense mutations in a well-characterized rat model of type 2 diabetes mellitus (DM2) result in decreased catalytic efficiency and a significant approximately 15 to 30% deficit in the degradation of both insulin and Abeta. Endogenously secreted Abeta(40) and Abeta(42) are significantly elevated in primary neuronal cultures from animals with the IDE mutations, but there is no increase in steady-state levels of rodent Abeta in the brain up to age 14 months. We conclude that naturally occurring, partial loss-of-function mutations in IDE sufficient to cause DM2 also impair neuronal regulation of Abeta levels, but the brain can apparently compensate for the partial deficit during the life span of the rat. Our findings have relevance for the emerging genetic evidence suggesting that IDE may be a late-onset AD-risk gene, and for the epidemiological relationships among hyperinsulinemia, DM2, and AD.
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PMID:Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. 1503 30

The incidence of type 2 diabetes mellitus (DM2) in children has increased worldwide and is commonly associated with overweight. Forty-four children with DM2 were studied by clinical histories, anthropometric measurements, and biochemical analysis. Homeostasis model assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) were determined to evaluate insulin resistance. Only five patients presented normal body mass index (BMI); the remainder were overweight, and 76% had acanthosis nigricans. Laboratory results yielded hyperglycemia, elevated glycosylated hemoglobin, insulin and C-peptide. Elevated HOMA-IR and decreased QUICKI values suggest insulin resistance. No significant difference was found between sexes, although overweight in girls had more influence over blood pressure and lipid levels (p <0.05). Time from diagnosis and HOMA-IR yielded relevant values (p = 0.010). Laboratory results, QUICKI, and HOMA-IR values suggested that these patients present DM2 and decreased insulin sensitivity. We recommend prevention of overweight and sedentary life-style.
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PMID:Type 2 diabetes mellitus in children--an increasing health problem in Mexico. 1505 52

A 13 year-old boy with Prader-Willi syndrome and steatohepatitis presented with diabetic ketoacidosis 4 weeks after the initiation of growth hormone (GH) treatment. He did not have signs or symptoms of type 2 diabetes mellitus (DM2) before the initiation of GH treatment. Hyperglycemia resolved 2 months after discontinuation of GH. He redeveloped DM2 6 months later associated with excessive weight gain. Diabetic ketoacidosis as a rare complication of GH therapy emphasizes the importance of screening for carbohydrate intolerance before and during GH treatment in patients with Prader-Willi syndrome. Steatohepatitis may be the only manifestation of insulin resistance and warrants further evaluation.
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PMID:Diabetic ketoacidosis secondary to growth hormone treatment in a boy with Prader-Willi syndrome and steatohepatitis. 1511 13

Several studies have demonstrated an association between low birth weight and impaired insulin sensitivity or even type 2 diabetes mellitus (DM2) in later life. Growth hormone (GH) is known to increase fasting and postprandial insulin levels. For that reason concern has been expressed regarding possible detrimental effects of GH therapy in children born SGA. In a Dutch trial the possible side effects of GH therapy on carbohydrate metabolism were assessed in short children born SGA after 6 years and at 6 months after discontinuation of GH therapy. This study included 79 prepubertal short children born SGA, participating in a multicenter double-blind, randomized, dose-response GH trial. Inclusion criteria were: 1) birth length SDS below -1.88, 2) age 3-11 years in boys and 3-9 years in girls, 3) height SDS < -1.88, 4) no spontaneous catch-up growth, and 5) an uncomplicated neonatal period. Mean (SD) value for age was 7.3 (2.1) years, birth length SDS -3.6, height SDS -3.0 (0.7) and BMI SDS -1.2 (1.3). All children were randomly assigned to either group A (n = 41) using 1 mg GH/m2/day or group B (n = 38) using 2 mg/m2/ d/ay (approximately 0.1 or 0.2 IU/kg/d, respectively). Standard oral glucose tolerance tests (OGTTs) were performed before and during 6 years of GH therapy and 6 months after discontinuation of GH therapy. Before GH therapy 8% of the children had impaired glucose tolerance (IGT) according to criteria of the WHO. After 6 years of GH therapy, IGT was found in 4% and after stopping GH in 10%. Mean fasting glucose increased significantly with 0.5 mMol/l after 1 year of GH therapy, without a further increase thereafter. GH therapy induced considerably higher fasting and glucose-stimulated insulin levels. None of the observed changes were different between the GH dosage groups. Children who remained prepubertal had similar glucose and insulin levels compared to children who entered puberty. HbA1c levels were always in the normal range and none of the children developed diabetes mellitus. After discontinuation of GH therapy the mean serum glucose levels remained normal and the mean serum insulin levels decreased significantly, to normal age reference values. Before the start of GH the mean systolic blood pressure was significantly higher compared to age-matched peers, whereas during GH therapy a significant decline in mean systolic blood pressure occurred, which remained similar after discontinuation of GH treatment. In conclusion, continuous, long-term GH therapy in short children born SGA has no adverse effects on glucose levels, even with GH dosages up to 2 mg/m2/day. However, as has been reported in other patient groups, GH induced higher fasting and glucose-stimulated insulin levels, indicating insulin resistance. After discontinuation of GH, serum insulin levels declined to normal age-matched reference levels. Since impaired insulin sensitivity and DM2 have been demonstrated in relatively young patients born SGA, long-term follow-up of children born SGA is advised, also after discontinuation of GH therapy.
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PMID:Small for gestational age (SGA): endocrine and metabolic consequences and effects of growth hormone treatment. 1513 8

As type 2 diabetes mellitus (DM2), obesity and sedentary lifestyles are increasing in developing countries, this observational study investigated the role of physical activity on DM2 in Jamaica. Anthropometry, body composition (by bioelectrical impedance analysis) and glucose tolerance status was assessed in 722 adults in 1993 and 1997. Energy expenditure was estimated in a subset using measured resting energy expenditure in combination with self-reported activity recalls. The rates of impaired glucose tolerance (IGT) were 23.7 and 27.3%, and DM2 were 16.3 and 23.7% among men and women, respectively. After adjusting for body composition, a one-unit increase in physical activity significantly reduced the odds of having diabetes (OR = 0.05; 95% CI: 0.004, 0.66), but not IGT. Hence, decreased physical activity is a significant independent contributor to the high rates of glucose intolerance in Jamaica. Efforts must be directed at minimizing obesity and increasing physical activity in developing countries.
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PMID:Energetic determinants of glucose tolerance status in Jamaican adults. 1516 40

The incidence of obesity and type 2 diabetes mellitus (DM2) in the United States has been increasing dramatically over the past 15 years, and is now at epidemic proportions. DM2 is the clinical manifestation of a long-term metabolic process that is initiated by cells' decreased sensitivity to the actions of insulin. Many outcome studies have identified DM2 as a strong and independent risk factor for the development of cardiovascular complications such as hypertension, arteriosclerosis, and heart failure. The goals of therapy in treating DM2 are to improve the long-term outlook for these patients. However, in selecting a therapeutic regimen for patients, clinicians should be aware that potentially severe adverse events may occur at a rate not previously identified in phase 3 studies. Certain therapies used to treat DM2, by effectively increasing the sensitivity of insulin, have also been reported to cause adverse effects, which can precipitate symptomatic heart failure. The purpose of this column is to discuss the therapeutic options available for treating patients with DM2, the potential pathophysiology of the adverse events of symptomatic heart failure, encouragement of use of the US Food and Drug Administration MedWatch program for reporting adverse events associated with medication therapy, and review of newer treatment guidelines for use of insulin-sensitizing agents in patients with chronic heart failure.
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PMID:Cardiovascular implications of thiazolidinedione therapy. 1524 73

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.
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PMID:Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity. 1527 Apr 3


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