Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poorly controlled insulin-dependent diabetes mellitus (IDDM) is associated with elevated basal plasma growth hormone (GH), disproportionally low insulin-like growth factor I (IGF-I) levels, and impaired somatic growth. These derangements in the GH-IGF axis imply a state of GH resistance. The mechanism of GH resistance is unknown; it may involve a defect at the level of the GH receptor, unresponsiveness due to a postreceptor defect in GH action, or both. To investigate a potential receptor involvement, we measured plasma high-affinity GH-binding protein (GHBP), which represents a truncated GH receptor and may reflect GH receptor levels in tissues, in patients with IDDM, patients with non-insulin-dependent diabetes (NIDDM), and nondiabetic control subjects. Patients with IDDM had significantly lower plasma GHBP levels than either patients with NIDDM or nondiabetic control subjects (mean value 18.2 vs. 24.6 and 23.8% GH bound/ml plasma, respectively, P less than 0.001). This difference persisted when only lean patients (less than 115% ideal body wt) were included in the analysis. Basal plasma GH levels were significantly elevated in IDDM compared with either patients with NIDDM or nondiabetic control subjects (mean 6.9 vs. 2.1 and 2.0 micrograms/L, respectively, P less than 0.001), whereas IFG-I levels were not significantly different in IDDM and NIDDM. No correlations were found between levels of GHBP and HbA1, duration of diabetes, or plasma GH. GHBP and IGF-I levels were significantly correlated in NIDDM but not in IDDM. We conclude that IDDM is associated with low GHBP levels and that GH resistance found in this disorder may be mediated, at least in part, by a decrease in GH receptor levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low plasma growth hormone binding protein in IDDM. 156 30

Recombinant DNA technology has made large amounts of insulin-like growth factor-I (IGF-I) available for studies in animal models and humans. It has been shown that treatment with IGF-I is associated with increased insulin sensitivity in normal subjects as well as in patients with growth hormone deficiency, Type 1 and Type 2 diabetes mellitus and type A insulin-resistance. The metabolic effects of IFG-I appear to be beneficial in these conditions. The reported side effects of IGF-I, which may be largely due to overdosage, have limited its use to small and mostly short-term clinical studies.
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PMID:Insulin-like growth factor-I in the therapy of non-insulin-dependent diabetes mellitus and insulin resistance. 876 73

To evaluate the role of insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) in excessive fetal growth (macrosomia) in diabetic pregnancy, 84 insulin-treated diabetic mothers and their infants were tested for serum concentrations of IGF-I, IFG-II, and IGFBP-1, -2 and -3. These parameters were correlated with the birth weight of neonates and placental weight. IGF-I and II levels were determined by specific radioimmunoassays (RIAs) after serum samples were extracted with aid-ethanol. IGFBPs were measured by Western immunoblot with specific antibodies to the respective IGFBP species. Serum concentrations of both IGF-I and IGF-II in mothers with either IDDM or NIDDM increased with the gestational period, reached a plateau at the third trimester, and returned to non-pregnant levels within 7 days after delivery. These values were not different from those in normal mothers before and throughout pregnancy. As previously reported, IGF-I concentrations in cord serum of neonates born to diabetic mothers were (P < 0.01) higher than those of newborns of normal mothers. Likewise, cord blood IGF-II levels were 2-fold higher in babies of diabetic mothers (P <0.001). Fetal IGF-I and IGF-II correlated with each other and with maternal HbA1C, and they positively correlated with either birth weight or placental weight. Cord IGFBP-3 concentrations were significantly higher in diabetic pregnancy, but IGFBP-2 concentrations were not different from those in normal pregnancy. Cord IGFBP-1 concentrations were significantly higher only in babies of mothers with IDDM. None of these cord IGFBP concentrations correlated with birth weight or placental weight. The data suggest that fetal IGF-II, like IGF-I, is involved in fetal and placental growth in diabetic pregnancy. The role of IGFBPs remained to be determined.
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PMID:Insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBP-1, -2 and -3) in diabetic pregnancy: relationship to macrosomia. 902 69

Japan Diabetes Society organized a committee for the revision of diagnostic criteria of diabetes mellitus in 1995. Like ADA and WHO reports, this committee adopts a classification based on etiologies, and presents a two-dimensional figure with etiologies and the state of insulin deficiency on different axis. The words IDDM and NIDDM will be retained as terms representing the different degree of insulin deficiency. On the basis of glycemia, diabetic type is defined when fasting plasma glucose exceeded 126 mg/dl and/or 2-hour plasma glucose by 75 g GTT exceeded 200 mg/dl. The diagnosis of diabetes in an individual can be made by confirming sustained diabetic type on repeated tests or co-existance of characteristic clinical features of diabetes. Normal type is defined by FPG < 110 mg/dl and 2hPG < 140 mg/dl. The borderline type, defined as neither normal nor diabetic types, corresponds to IFG plus IGT according to ADA and WHO reports. The application of HbA1c for diagnosis of diabetes and the criteria for gestational diabetes mellitus are also discussed.
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PMID:[Outline of revision of classification and diagnostic criteria of diabetes mellitus in Japan]. 1019 34

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.
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PMID:Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus. 1131 22

In a cross-sectional study, we assessed beta-cell function and insulin sensitivity index (ISI) with hyperglycemic clamps (10 mmol/l) in 24 subjects with impaired fasting glycemia (IFG, fasting plasma glucose [FPG] between 6.1 and 7.0 mmol/l), 15 type 2 diabetic subjects (FPG >7.0 mmol/l), and 280 subjects with normal fasting glycemia (NFG, FPG <6.1 mmol/l). First-phase insulin release (0-10 min) was lower in IFG (geometric mean 541 pmol/l.10 min; 95% confidence interval [CI] 416-702 pmol/l.10 min) and in type 2 diabetes (geometric mean 376 pmol/l.10 min; 95% CI 247-572 pmol/l.10 min) than NFG (geometric mean 814 pmol/l.10 min; 95% CI 759-873 pmol/l.10 min) (P < 0.001). Second-phase insulin secretion (140-180 min) was also lower in IFG (geometric mean 251 pmol/l; 95% CI 198-318 pmol/l; P = 0.026) and type 2 diabetes (geometric mean 157 pmol/l; 95% CI 105-235 pmol/l; P < 0.001) than NFG (geometric mean 295 pmol/l; 95% CI 276-315 pmol/l). IFG and type 2 diabetic subjects had a lower ISI (0.15 plus minus 0.02 and 0.16 plus minus 0.02 micromol/kg fat-free mass [FFM]/min/pmol/l, respectively) than NFG (0.24 plus minus 0.01 micromol/kg FFM/min/pmol/l, P < 0.05). We found a stepwise decline in first-phase (and second-phase) secretion in NFG subjects with progressive decline in oral glucose tolerance (P < 0.05). IFG subjects with impaired glucose tolerance (IGT) had lower first-phase secretion than NFG subjects with IGT (P < 0.02), with comparable second-phase secretion and ISI. NFG and IFG subjects with a diabetic glucose tolerance (2-h glucose >11.1 mmol/l) had a lower ISI than their respective IGT counterparts (P < 0.05). We conclude that the early stages of glucose intolerance are associated with disturbances in beta-cell function, while insulin resistance is seen more markedly in later stages.
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PMID:Disturbances in beta-cell function in impaired fasting glycemia. 1181 91

Diabetes mellitus is a heterogeneous disorder. Evidence for heterogeneity is based on measuring endogenous insulin level since some forty years ago. Insulin is lacking at the time of diagnosis in most patients, whose disease started rapidly, with classical symptoms, and who are mainly children, adolescents or young adults. In the majority of middle-aged, obese diabetics, insulin levels are frequently high at diagnosis. Since insulin measuring from sera became a routine laboratory test these two main types were nominated as insulin-dependent, and insulin non-dependent types (IDDM and NIDDM). The aim of the recent classification was, that different diabetic subgroups should be based on etiologic evidence. (Previous classification was based mainly due to the current therapy!). To avoid confusing nominations, the recent classification recommended to abandon the acronyms, IDDM and NIDDM, and only type-1 and type-2 should be used In the third subgroup-other diabetic groups--there are selected many disorders, whose etiology is mostly clear. As fourth subgroup gestational diabetes preserved its previous place. There are some differential-diagnostic problems in between type-1 and type-2 subgroups, especially between lean body weight type-2 and-the newly discovered latent-onset diabetes in adults (LADA). Diagnostic criteria of diabetes and prediabetic states are being changed according to epidemiological data, because type-2 patients die frequently from cardio-cerebrovascular fatal disorders, and elevated blood sugar values-especially postprandially-contribute to it. Thresholds of blood sugar values for diagnosing diabetes are therefore decreasing, and a new category: impaired fasting glucose (IFG, blood sugar: 6, 1-7.0 mmol/l) was introduced. Impaired glucose tolerance (IGT) remained as prediabetic state. IGT + IFG are nominated as impaired glucoregulation. These two categories cover different populations. Oral glucose loading test in most problematic cases should be carried out. The clinical importance of postprandial hyperglycaemia (postprandial state) is discussed. As a new clinical concept, the Metabolic Syndrome seems to replace type-2 diabetes in the majority of these patients, even in the impaired glucose tolerance (IGT) state. Diabetics, carrying the features of this syndrome need holistic care.
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PMID:[New diagnostic and classification system in diabetic syndrome]. 1250 59

Type 2 diabetes is characterized by impaired insulin secretion. Some but not all studies suggest that a decrease in beta-cell mass contributes to this. We examined pancreatic tissue from 124 autopsies: 91 obese cases (BMI >27 kg/m(2); 41 with type 2 diabetes, 15 with impaired fasting glucose [IFG], and 35 nondiabetic subjects) and 33 lean cases (BMI <25 kg/m(2); 16 type 2 diabetic and 17 nondiabetic subjects). We measured relative beta-cell volume, frequency of beta-cell apoptosis and replication, and new islet formation from exocrine ducts (neogenesis). Relative beta-cell volume was increased in obese versus lean nondiabetic cases (P = 0.05) through the mechanism of increased neogenesis (P < 0.05). Obese humans with IFG and type 2 diabetes had a 40% (P < 0.05) and 63% (P < 0.01) deficit and lean cases of type 2 diabetes had a 41% deficit (P < 0.05) in relative beta-cell volume compared with nondiabetic obese and lean cases, respectively. The frequency of beta-cell replication was very low in all cases and no different among groups. Neogenesis, while increased with obesity, was comparable in obese type 2 diabetic, IFG, or nondiabetic subjects and in lean type 2 diabetic or nondiabetic subjects. However, the frequency of beta-cell apoptosis was increased 10-fold in lean and 3-fold in obese cases of type 2 diabetes compared with their respective nondiabetic control group (P < 0.05). We conclude that beta-cell mass is decreased in type 2 diabetes and that the mechanism underlying this is increased beta-cell apoptosis. Since the major defect leading to a decrease in beta-cell mass in type 2 diabetes is increased apoptosis, while new islet formation and beta-cell replication are normal, therapeutic approaches designed to arrest apoptosis could be a significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia.
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PMID:Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. 1250 99

This study compared the relative role of insulin resistance and beta-cell dysfunction (both assessed using the HOMA method) with glucose intolerance conditions in the progression to type 2 diabetes among a high risk group of subjects with fasting plasma glucose (FPG) 5.6-7.0 mmol/l in Kinmen, Taiwan. Data were collected during a continuing prospective study (1998-99) of a group of Taiwanese subjects at high-risk of developing type 2 diabetes who had fasting hyperglycemia (5.6-7.0 mmol/l) and exhibited 2-h postload glucose concentrations <11.1 mmol/l from 1992-94 to 1995-96. Among 644 non-diabetic subjects at baseline, 79.8% (514/644) had at least one follow-up examination. There were 107 new cases of diabetes diagnosed by 1999 WHO criteria in 2918.7 person-years of follow-up. The incidence rate was 3.67%/year (107/2918.7). After adjustment for other possible associative variables, including gender, age, BMI, waist circumference, insulin resistance, and beta-cell dysfunction, Cox's hazard model showed that those individuals with isolated IFG (impaired fasting glucose) and those individuals with isolated IGT (2-h glucose impairment) exhibited similar risk of developing diabetes. Those individuals with isolated IFG and isolated IGT showed a comparable impairment of basal or hepatic insulin sensitivity, but those individuals with isolated IFG had a greater beta-cell dysfunction by the HOMA method.
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PMID:Relative role of insulin resistance and beta-cell dysfunction in the progression to type 2 diabetes--The Kinmen Study. 1259 20

The study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM) is a 3 years randomised clinical trial designed to evaluate the effect of a combined diet and physical activity intervention program on glucose tolerance in a Dutch population at increased risk for developing type 2 diabetes. Here the design of the lifestyle-intervention study is described and results are presented from the preliminary population screening, conducted between March 1999 and June 2000. In total, 2,820 subjects with an increased risk of having disturbances in glucose homeostasis (i.e. age >40 years and BMI>25 kg/m(2) or a family history of diabetes) underwent a first oral glucose tolerance test (OGTT). Abnormal glucose homeostasis was detected in 826 subjects (30.4%): 226 type 2 diabetes (type 2DM, 8.3%), 215 impaired fasting glucose (IFG, 7.9%) and 385 impaired glucose tolerance (IGT, 14.2%). Both increasing age and BMI were strongly related to the prevalence of IGT and diabetes. After a second OGTT, 114 subjects with glucose intolerance and in otherwise good health were eligible for participation in the intervention study (SLIM). The high prevalence of disturbances in glucose homeostasis observed in the preliminary screening underscore the importance of early (lifestyle) interventions in those at risk for developing diabetes. SLIM will address this topic in the Dutch population.
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PMID:Study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM): design and screening results. 1284 23


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