Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both impaired glucose tolerance (IGT) (as defined by the 1985 World Health Organization criteria) and impaired fasting glucose (IFG) (as defined by the 1997 American Diabetes Association criteria) represent intermediate metabolic states between normal and diabetic glucose homeostasis. Cardiovascular disease may be related to postglucose load rather than fasting glycemia, i.e., IGT rather than IFG. We hypothesized that subjects with IGT may be more insulin resistant and have higher levels of common cardiovascular risk factors than those with isolated IFG. In the Insulin Resistance Atherosclerosis Study (IRAS), we studied S(i) and first-phase insulin secretion (acute insulin response [AIR]), as derived from a frequently sampled intravenous glucose tolerance test, as well as common cardiovascular risk factors in four different glucose tolerance categories (NFG/NGT [n = 654], NFG/IGT [n = 255], IFG/NGT [n = 59], and IFG/IGT [n = 102]) among nondiabetic subjects. Subjects with isolated postchallenge hyperglycemia (NFG/IGT) had lower S(i) (means +/- SE: 2.10 +/- 0.04 vs. 2.59 +/- 0.13 x 10(-4) min(-1). microU(-1). ml(-1); P = 0.005), lower proinsulin levels (34.4 +/- 1.8 vs. 42.0 +/- 4.5 pmol/l; P = 0.03), higher AIR (273.1 +/- 18.1 vs. 215.9 +/- 30.0 pmol/l; P = 0.04), higher C-reactive protein (2.49 +/- 0.3 vs. 1.49 +/- 0.5 mg/l; P = 0.0015), and higher triglyceride levels (137.7 +/- 5.5 vs. 108.4 +/- 8.9 mg/dl; P = 0.0025) than subjects with isolated fasting hyperglycemia (IFG/NGT). The relation of insulin resistance to glucose tolerance category was consistently seen in women and men and across the three ethnic groups of the IRAS (non-Hispanic whites, African Americans, and Hispanics). Nondiabetic individuals with isolated postchallenge hyperglycemia (IGT) are more insulin resistant than individuals with isolated fasting hyperglycemia (IFG). The risk factor pattern (including increased insulin resistance) seen in isolated IGT identifies a subgroup of nondiabetic individuals who are likely to benefit from early intervention.
Diabetes 2004 Jun
PMID:Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. 1516 60

The aim of the present study was to describe the associations between glucose tolerance and symptoms in an unselected non-institutionalised elderly population aged 73 years or over (n = 259, of whom 93 were men). Diabetes was assessed on the basis of self-reports and 2-h oral glucose tolerance tests (1985 WHO criteria). Symptoms were measured with a modified diabetes symptom checklist (DSC-Type 2). The previously diagnosed diabetic patients reported to have more symptoms in all the six dimensions of the symptom checklist than the other study groups. According to the responses to twenty out of 34 items, more of the previously diagnosed diabetic women had symptoms than the other female study groups; the corresponding figure for the previously diagnosed diabetic men being 16/34. The following hyperglycaemic symptoms: "dry mouth", "increasing fatigue in the course of the day", "numbness in the hands", were either weakly or significantly associated with undiagnosed diabetes. Men with IGT reported to have "dry mouth" and "tingling or pricking in the legs or feet" more often than men with NGT. Symptoms of "moodiness" increased along with the deterioration of glucose tolerance, and it seems that depression is associated with type 2 diabetes in elderly people, too. Although the study covered a wide range of symptoms, it did not clearly reveal such symptoms that could be used as potential indicators of undiagnosed diabetes or especially IGT among elderly patients.
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PMID:Does hyperglycaemia cause symptoms in elderly people? 1524 24

We have examined the contribution of insulin secretion and insulin resistance to glucose intolerance in Japanese. Some indices of insulin secretion and insulin sensitivity based on the results of OGTT were used. The decline of insulin secretion capacity was significant throughout the development of glucose intolerance from NGT via IGT to DM. Decreased insulinogenic indices were conspicuous when it is compared with other types of diabetes. Slight impairment of insulin secretion has begun in subjects with NGT. The progression from NGT via isolated IGT to isolated post-challenge hyperglycemia was considered mostly due to the deterioration of early-phase insulin secretion. It is summarized that decreased insulin secretion capacity takes a definite role in the development from NGT to type 2 diabetes in Japan.
Diabetes Res Clin Pract 2004 Dec
PMID:Insulin secretion capacity in the development from normal glucose tolerance to type 2 diabetes. 1556 78

The aim of this study was to determine the association between type-2 diabetes mellitus (DM), BMD and fractures in 6,655 men and women aged 55 years and over from the Rotterdam Study. We compared subjects with type-2 DM to subjects without DM. Additionally, subset analyses were performed, dividing subjects on the basis of the glucose tolerance test into already treated DM, newly diagnosed DM, impaired glucose tolerance (IGT) and normal glucose tolerance (NGT, reference). Femoral neck and lumbar spine BMD were measured using DEXA. Nonvertebral fracture ascertainment was performed using an automated record system involving GPs and local hospitals. Although subjects with DM had higher BMD, they had an increased nonvertebral fracture risk: hazard ratio (HR) 1.33 (1.00-1.77). In subset analysis, the increased fracture risk appeared restricted to treated DM subjects only: HR 1.69 (1.16-2.46). Subjects with IGT had a higher BMD, but contrary to treated DM, they had a lower fracture risk: HR 0.80 (0.63-1.00). In conclusion, subjects with type-2 DM and IGT both have a higher BMD. Whereas, subjects with IGT have a decreased fracture risk, subjects with DM (primarily those with already established and treated DM) had an increased fracture risk, probably due to long-term complications associated with DM.
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PMID:Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam Study. 1594 Mar 95

Glucagon is the physiological antagonist of insulin. Postprandial (pp) hyperglycemia in impaired glucose tolerance (IGT) and in type 2 diabetes mellitus (T2DM) may also depend on irregularities in glucagon secretion. This study investigated the glucagon excursion after a lipid-glucose-protein tolerance test in subjects with different stages of glucose intolerance. We also analyzed the relationship between pp glucagon secretion and hyperglycemias. A total of 64 men (27 healthy subjects with normal glucose tolerance [NGT], 15 with IGT, and 22 with T2DM) were examined. Plasma glucose (PG), insulin, proinsulin, free fatty acids, and triglycerides were measured in the fasting state and at 30 minutes and 2, 3, 4, and 6 hours after the intake of the test meal, which contained 126 g carbohydrates, 92 g fat, and 17 g protein. Postprandial concentrations of metabolic parameters were calculated as area under the curve (AUC). Glucagon was measured in the fasting state and at 30 minutes and 2 and 4 hours pp. Early glucagon increment was defined as glucagon at 30 minutes minus fasting glucagon. The insulin response was quantified as insulin increment divided by PG increment in the corresponding time. Insulin resistance was calculated using lomeostasis model assessment (HOMA). Fasting glucagon was significantly increased in IGT vs NGT (P<.05), and early glucagon increment was significantly higher in T2DM vs NGT and IGT (P<.05). The 2-hour glucagon concentration after the load (AUC) was increased in IGT and T2DM vs NGT (P<.05). Early glucagon increment and the 2-hour AUC of glucagon were strongly correlated to pp glycemia (r=0.494 and P=.001, and r=0.439 and P=.003, respectively). An inverse correlation was observed between early glucagon increment and insulin response at 30 minutes and 2 hours after the meal load (r=-0.287 and P=.026, and r=-0.435 and P=.001, respectively). The 2-hour AUC of glucagon was significantly associated with insulin resistance (r=0.354, P=.020). Multivariate analysis revealed 2-hour insulin response and early glucagon increment as significant independent determinants of the AUC of PG in IGT (R=0.787). In T2DM, 2-hour insulin response, insulin resistance, and early glucagon increment were significant determinants of the AUC of PG (R=0.867). Our study suggests an important role for the irregularities in glucagon response in the pp glucose excursion after a standardized oral mixed meal in IGT and in T2DM. According to our data, a bihormonal imbalance starts before diabetes is diagnosed. Prospective studies are needed to evaluate the impact of glucagon on the progression of glucose intolerance and the possible effects of medicinal suppression of glucagon increment to prevent the progression of glucose tolerance.
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PMID:Impact of glucagon response on postprandial hyperglycemia in men with impaired glucose tolerance and type 2 diabetes mellitus. 1612 28

The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes-associated single nucleotide polymorphism (SNP)-43 G/G genotype had reduced CAPN10 mRNA levels compared with subjects carrying the SNP-43 A-allele. Age had no significant influence on CAPN10 mRNA levels. Insulin had no significant effect on CAPN10 mRNA levels, neither in the twins nor in the basal state of the Intralipid study. However, after a 24-h infusion of Intralipid, we noted a significant increase in CAPN10 mRNA in response to insulin in subjects with NGT but not in subjects with IGT. In conclusion, we provide evidence that mRNA expression of CAPN10 in skeletal muscle is under genetic control. Glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat.
Diabetes 2005 Oct
PMID:Genetic and nongenetic regulation of CAPN10 mRNA expression in skeletal muscle. 1618 7

To investigate the pathogenesis of distal pancreatectomy (d-Px)-induced diabetes in Korean patients, we investigated insulin secretory and sensitivity indexes obtained by oral glucose tolerance testing in 20 patients that had received d-Px (10 with d-Px-induced diabetes and 10 with normal glucose tolerance with d-Px [NGT d-Px]) and in 164 control subjects (77 with type 2 diabetes mellitus and 87 with NGT) that did not receive d-Px. The pancreatectomized subjects had lower fasting serum insulin, homeostasis model assessment of pancreatic beta-cell function (HOMA-beta) levels, and insulinogenic indices than the NGT controls. The HOMA-beta values of nonobese NGT d-Px- and d-Px-induced diabetic subjects were 73.7% and 38.7% of those for nonobese NGT controls, respectively, and HOMA-beta was significantly lower only for d-Px-induced diabetic subjects (P < .01). In obese subjects, the HOMA-beta values of obese d-Px-induced diabetic subjects were significantly lower than those of obese NGT controls (P < .05). The insulin sensitivity was significantly lower in nonobese type 2 diabetes mellitus controls than in nonobese NGT d-Px or in nonobese d-Px-induced diabetic subjects (P < .001 and .05, respectively). These results show that a reduced insulin secretory function is a typical feature of glucose homeostasis in distal pancreatectomized patients and that insulin secretory defect plays a major role in the development of diabetes in these patients. In addition, the study suggests that pancreatic resections of 60% or less and body mass index are not the main causes of diabetes onset after d-Px in this study.
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PMID:Insulin secretory defect plays a major role in the development of diabetes in patients with distal pancreatectomy. 1632 32

Diabetes mellitus (DM) and abnormal glucose tolerance (IGT) are common in cystic fibrosis (CF). The loss of pancreatic beta-cells due to pancreatic fibrosis is thought to be one of the principal causes of diabetes in CF, but the aetiology of DM remains somewhat puzzling. Genetic factors may contribute to the development of CF related diabetes (CFRD). The purpose of this study was to investigate the role of polymorphisms in six genes on IGT or DM incidence. PCR and dHPLC were used to screen DNA samples for polymorphisms. Using 2-h oral glucose tolerance tests, 163 adult pancreatic insufficient CF patients have been subdivided in 3 groups: 54 NGT (normal glucose tolerance), 33 IGT and 76 CFRD. We found the first evidence for the association between CFRD and UCSNP-19 polymorphism in the CAPN10 gene. The UCSNP-19 genotype distribution differed significantly between NGT, IGT and CFRD groups. The difference reflected an increase in the 22 genotype (3 copies of 32-bp sequence) in IGT and CFRD patients (p=0.05). Odds ratio for the homozygote 22 versus homozygote 11 was 3.4 (p=0.02). All allele and genotype distributions for the other polymorphisms were similar in the three groups. In conclusion, our observations suggest that UCSNP-19 of CAPN10 may be involved in the pathogenesis of diabetes in CF.
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PMID:Calpain 10 and development of diabetes mellitus in cystic fibrosis. 1637 60

The aim of the study was to describe serum adiponectin levels in a population-based sample of women with different degrees of glucose tolerance and to examine if the variability in serum adiponectin was explained by family history of diabetes, obesity, insulin resistance, glycemia, and inflammation. Repeated oral glucose tolerance tests were used in a screening procedure of a cohort of 64-year-old women to identify those with diabetes mellitus n = 210) and impaired glucose tolerance (n = 201). A random sample of women with normal glucose tolerance (NGT, n = 186) was also included. The examination included history of first-degree relatives with diabetes, anthropometry, measurement of circulating adiponectin, glutamic acid decarboxylase antibodies, blood glucose, HbA1c, insulin, proinsulin, C-peptide, high-sensitivity C-reactive protein, and homeostasis model assessment. Serum adiponectin concentration was lowest among diabetic women, highest in the random-sample NGT group, and intermediate in the impaired glucose tolerance group. This difference was partly explained by homeostasis model assessment, C-peptide, family history, and high-sensitivity C-reactive protein (R2 = 0.33, P < .001), but obesity and glycemia did not contribute to this variability in serum adiponectin. A family history of diabetes was associated with low serum adiponectin concentration independently of obesity, glycemia, or insulin sensitivity (P = .002). Glutamic acid decarboxylase-positive diabetic women (n = 17) had similar serum adiponectin as the NGT group in spite of hyperglycemia. In conclusion, serum adiponectin was lowered in women with type 2 diabetes mellitus, and this difference could only be partly explained by insulin resistance, insulin secretion, family history of diabetes, and inflammation. Family history of diabetes was independently associated with hypoadiponectinemia. Autoimmune diabetic women did not have low adiponectin levels.
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PMID:Serum adiponectin in a population sample of 64-year-old women in relation to glucose tolerance, family history of diabetes, autoimmunity, insulin sensitivity, C-peptide, and inflammation. 1642 25

This study was conducted to observe changes in insulin secretion and insulin action in subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). A total of 319 subjects were studied with an oral glucose tolerance test (OGTT). Fasting plasma glucose and insulin concentrations were measured at baseline and every 30 min during the OGTT. Fifty-eight subjects also received a euglycemic-hyperinsulinemic clamp. Insulin sensitivity was calculated as the total glucose disposal (TGD) during the last 30 min of the clamp. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated from fasting plasma glucose and insulin concentrations. Subjects with IFG had TGD similar to normal glucose-tolerant subjects, while subjects with IGT and combined IFG/IGT had significantly reduced TGD. HOMA-IR in subjects with IFG was similar to that in subjects with combined IFG/IGT and significantly higher than HOMA-IR in subjects with IGT or NGT. Insulin secretion, measured by the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) and by the ratio of the incremental area under the curve (AUC) of insulin to the incremental AUC of glucose (0-120 min), was reduced to the same extent in all three glucose-intolerant groups. When both measurements of beta-cell function were adjusted for severity of insulin resistance, subjects with IGT and combined IFG/IGT had a significantly greater reduction in insulin secretion than subjects with IFG. Subjects with IGT and IFG have different metabolic characteristics. Differences in insulin sensitivity and insulin secretion may predict different rates of progression to type 2 diabetes and varying susceptibility to cardiovascular disease.
Diabetes 2006 May
PMID:Insulin secretion and action in subjects with impaired fasting glucose and impaired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study. 1664 1


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